A significant plot element is House's use of Vicodin to manage pain. Five years before the start of the series, House suffered an infarction in his leg. However, House is very reluctant to talk about the incident which damaged his leg and can be easily offended when it is brought up.

　　But still, the truth is to be uncovered.

　　Unfortunately, the only symptom of the infarction in his leg was leg pain, and by the time House himself realized that he was suffering from muscle death, the leg was in such a bad state that amputation was the recommended course of action. However, House rejected the suggestion and instead underwent a procedure to bypass circulation around the dead muscle. The result was intense pain during the healing process, which nearly resulted in cardiac arrest until House was put into a chemically induced coma. However, while House was comatose, Stacy, acting as his medical proxy decided to go with Dr. Cuddy's suggestion to have the dead muscle surgically removed. Although this most likely saved House's life, it left him with permanent intense pain in his right leg. The wound on his leg still bears an obvious scar from where the muscle was removed and there is a divot in his skin where the muscle used to be.

　　House's anger over Stacy's decision not to trust him poisoned the relationship and led to Stacy leaving. House started to lean heavily on Wilson for emotional support, eventually leading in part to Wilson's divorce from his second wife Bonnie Wilson. House's condition is most likely made worse by the fact that prior to the infarction, he was quite an active athlete, engaging in golf and running on a regular basis.

　　As a result of the pain, House became addicted to the narcotic pain killer Vicodin. It should be noted, however, that even before his disability, House admitted to recreational drug use. Although House realized he was addicted, he believed the Vicodin was the only thing that would allow him to overcome the pain and allow him to function. His dependence on the drug got him into trouble on several occasions, and his colleagues are unsure whether House's anti-social personality traits are the result of his addiction, his pain, or his underlying personality.

　　In Season 1 of House M.D. DVD Box Set, House admits he is addicted to Vicodin, but says he does not have a problem because the pills "let me do my job, and they take away my pain"