2006
Marlena’s memory returned, and she and John left Salem for a while. However, she needed a separation from John so she could sort her life out. John soon suspected that she disappeared and went to New Jersey in search of her. He found her in a cart tied up and the two were happily reunited. Upon returning to Salem, they discovered that Steve and Kayla Johnson had been poisoned by a rare biotoxin, courtesy of the mysterious gloved hand crimes. They flew off to Canada to retrieve the cure for Kayla. When Marlena jumped from the plane and landed in the snow she was rescued by none other than Smokey Robinson. John soon found her and the two shared a romantic dance in Smokey’s cabin while he sang for them. The two soon returned to Salem with the cure.
John and Marlena traveled to Italy, since they suspected that Stefano DiMera was still alive. They had a romantic private wedding ceremony in Italy and made a wish on an Italian coin. They were stunned to discover Stefano alive, but deathly ill. Upon returning to Salem, E.J. Wells shot John in December of 2006 and John lingered in a coma for the next five months. During his coma, E.J. forced Steve Johnson to take John’s kidney, since Stefano needed one.
2007
John finally woke up from his coma in May. He and Marlena were reunited again and spent much of that summer reading ancient love letters between Santo DiMera and Colleen Brady. It was revealed during this time that the real Tony DiMera had been living on an island for the past twenty years, courtesy of Stefano. Evil Andre DiMera had impersonated Tony and taken over his life, which meant that Andre was the one who married Kristen and framed John for his "murder," among other dastardly things.
John’s life came to a sudden halt when he was run down by a hit and run driver in October of 2007. Marlena was horrified to witness the incident. John was rushed to the hospital and suffered massive internal injuries. On October 17, 2007, John took his last breath and passed away.
2008
In January, Marlena was shocked to discover John alive in Dr. Rolf and Stefano’s basement. John was the mysterious patient whom Stefano had programmed to carry out a mission. Unfortunately, John had no memory of his past life or the love he shared with Marlena. He was no longer the same kind, loving, generous man as before. He was cold, selfish, and sarcastic, and tests at the hospital proved that he was incapable of feeling emotion. John was only concerned with carrying out his mission, which was to kill Stefano’s nemesis: Colleen Brady.
John convinced Marlena to take him to Ireland. Bo, Hope, Steve, Kayla, Shawn, Belle, Philip, and Chloe were among the other Salemites to venture to Ireland since Claire had been kidnapped and taken there. They were stunned to discover Colleen Brady alive after all! She had been presumed dead when everyone thought she committed suicide and jumped off a cliff to her death. John tried to kill Collen until she dropped a bomb on him: he was hers and Santo DiMera's son. It turns out that Colleen didn't have enough money to support John, or "Ryan" as she named him, so she visited him at the orphanage before he was adopted by the Alamains. Colleen soon died in John's arms after begging him to hold her one last time. John was stunned when he displayed a tad bit of emotion.
John and the other passengers boarded his private jet to return to Salem. However, he soon discovered that the plane had been sabotaged and the pilots drugged. Everyone’s lives were at stake and depended on John to save them and land the plane. The plane crash landed somewhere in Greenland. Unfortunately, Grandpa Shawn heroically passed away giving up his oxygen mask for Bo. John bonded with his granddaughter Claire while awaiting rescue, and he and Marlena ended up making love! He told her how great the sex between them was, but still didn’t remember her. Marlena affirmed that he would get no more sex from her until he regained his memory.
John soon became involved in a power struggle with the Kiriakises in the shipping industry, taking over the DiMera empire since Stefano was currently out of commission. Paul Hollingsworth was newly divorced and broke and took a job as a field director of the customs department, working on the docks. John secretly bribed Paul into delaying and impounding the Kiriakis shipments. As a result, Paul got caught in the middle of the turf war between John and the Kiriakises.
Little did John initially know that Paul was also taking a bribe from Philip, who paid Paul to plant cocaine on John’s ships. John soon uncovered a disk hidden in the safe at the DiMera mansion which contained all of his past memories. Soon afterwards, he found that the disk was encrypted, and Philip paid someone to break into the mansion and steal the disc. Philip was unable to break the encryption on the disk, but learned that the disk contained brainwaves.
John was soon arrested for drug trafficking and for assaulting a police officer, Roman. When John became belligerent and resisted arrest, Marlena felt as though she had no choice but to inject him with drugs. John was furious and continued to insist that Philip set him up. Marlena begged Roman not to lock John up, rehashing what was done to him in Rolf’s lab at the DiMera mansion. She stood by John and believed in his innocence.
Marlena paid John's bail and left town soon afterwards. John was still under suspicion for drug trafficking and felt all alone with nobody on his side and everyone wishing he was the "old" John. He soon encountered Ava Vitali on the docks and began dating her, even though he was still legally married to Marlena. John liked the fact that Ava accepted him for the person he was and didn't try to change him.
John soon learned that the warehouse containing all the goods impounded from his ship burned down. He immediately suspected none other than Philip. As it turned out, not only did Philip pay Paul Hollingsworth to plant drugs onto John’s ship, but Paul acted outside of Philip's orders and set John's impounded warehouse on fire. Paul's body was soon rolled into the river and it appeared as though he was dead.
