Which fictional detective is Gregory House most directly modeled on in House M.D.?

Gregory House is most directly modeled on Sherlock Holmes in House M.D. Both characters rely on observation, deduction, unusual hypotheses, and a willingness to challenge ordinary explanations.

The connection appears in several details. House's surname echoes Holmes's, James Wilson parallels Holmes's friend Dr. John Watson, and the address 221B Baker Street is referenced through House's apartment number. House also plays the piano, while Holmes is associated with the violin.

The medical setting transforms detective fiction's crimes into diagnostic mysteries. Instead of identifying a culprit, House identifies a disease. The show's creators used the Holmes influence as a framework, while giving House distinct medical expertise, chronic pain, addiction struggles, and conflicts with hospital colleagues.