Preclinical studies suggest that statins contribute to the prevention of pancreatic cancer; however, the results of epidemiologic studies are inconsistent. Furthermore, sufficient data are unavailable for the general population of Asia. Here, we conducted an observational study using a comprehensive patient-linked, longitudinal health insurance database comprising the records of 2,230,848 individuals residing in Shizuoka Prefecture, Japan, from April 2012 to September 2018. We included individuals older than 40 years with data for medical examinations and statin exposure (≥365 statin prescription days). To balance baseline characteristics between the statin exposure and statin nonexposure groups, we used inverse probability of treatment propensity score weighting method. We estimated hazard ratios for associations with pancreatic cancer using the Cox proportional hazards regression model. Among 2,230,848 individuals, we included 100,537 in the statin exposure group (24%) and 326,033 in the statin nonexposure group (76%). Among the statin exposure group (352,485 person-years) and the statin nonexposure group (1,098,463 person-years), 394 (1.12 per 1,000 person-years) and 1176 (1.07 per 1,000 person-years) developed pancreatic cancer, respectively (P = 0.464). After adjustments using inverse probability of treatment weighting, the statin exposure group was associated with a decreased incidence of pancreatic cancer (hazard ratio, 0.84; 95% confidence intervals, 0.72–0.99; P = 0.036). In conclusion, the current Japanese regional population-based cohort study shows that statin exposure was associated with a lower incidence of pancreatic cancer.Prevention Relevance:This study may support the possible role of statins in preventing pancreatic cancer in the general population in Japan.