The physician and literary writer Silas Weir Mitchell had a long-standing interest in venom research, spanning the second half of the nineteenth century. Mitchell’s work showcases the dynamics of medical and methodological thought during a key period in the history of the biomedical sciences, just like Mead’s Mechanical Account of Poisons did for the eighteenth century. Venom research was situated at the intersection of several areas of biomedical investigation—including toxicology, physiology, medical chemistry, and therapeutics. The chapter shows how Mitchell appropriated experimental approaches from various fields to characterize both the cause and the effects of the disease caused by snake venom. The chapter also highlights the shift of emphasis in the methodology of experiments from variations of experimental procedures to comparative tests and checks. At that time, comparative experimentation was explicitly discussed both in the life sciences and in the emerging philosophy of science. However, the scientists’ discussions were driven by pragmatic concerns and thus differed significantly from systematic accounts of comparative experimentation such as Herschel’s and Mill’s philosophies of science.