This paper explores the introduction of smallpox variolation (人痘法) as a means of addressing the smallpox epidemic during the Edo period in Japan. It also investigates the impact of smallpox variolation on Japanese society during the late Edo period. I begin by outlining the history of smallpox epidemics in Japan. Subsequently, I document the process of introducing and developing smallpox variolation, which was considered a valuable preventive measure against smallpox during that period. While smallpox variolation was introduced in the mid-18th century, it took about half a century for the practice to be effectively implemented. Several physicians attempted variolation during this period, but Ogata Shunsaku (緖方春朔) was renowned as the first to succeed on a large scale, particularly with children. He authored works such as “Shutohissunben (種痘必順辨)” to advocate for the effectiveness of variolation. Additionally, rather than simply adopting the Chinese method of variolation, he developed his own method that took into consideration Japan's unique climate and environment, hoping to enhance the efficacy of variolation. During that time, the prevailing response to the smallpox epidemic focused on diagnosis and treatment using medicine rather than variolation. While Ogata Shunsaku actively practiced variolation, the shogunate established an institution within the medical department tasked with the prevention and treatment of smallpox. This institution propagated the Ikeda-ryu (池田流) method, which specialized in diagnosing and treating smallpox. Despite disparities in approaches, competition between smallpox prevention and treatment catalyzed the accumulation of relevant medical knowledge and experience in Japan during the early 19th century. Initially, variolation was introduced from China; however, over time, researchers experimented with it in various ways, integrating knowledge from Rangaku (蘭學) and cowpox inoculation (牛痘法). Responding to academic and technical developments, Ranpoi (蘭方醫) made diverse attempts at variolation that served as precursors to the eventual adoption of cowpox inoculation. Examining the process of variolation’s introduction and implementation elucidates the characteristics of early 19th-century Japanese medicine that transcended disciplinary boundaries.