Introduction: Studies have suggested that statins may inhibit tumor cell growth and possibly prevent carcinogenesis. The objective of this study was to investigate the association between persistent statin use and the risk of primary cancer in adults. Methods: This retrospective study was conducted by using the computerized data sets of a large health maintenance organization (HMO) in Israel. The study population was 202,648 enrollees aged 21 or older who purchased at least 1 pack of statin medication from 1998 to 2006. The follow-up period was from the date of first statin dispensation (index date) to the date of first cancer diagnosis, death, leaving the HMO, or September 1, 2007, whichever occurred first. Persistence was measured by calculating the mean proportion of follow-up days covered (PDC) with statins by dividing the quantity of statin dispensed by the total follow-up time. Results: During the study period, 8,662 incident cancers were reported. In a multivariable model, the highest cancer risk was calculated among nonpersistent statin users. A strong negative association between persistence with statin therapy and cancer risk was calculated for hematopoietic malignancies, where patients covered with statins in 86% or more of the follow-up time had a 31% (95% confidence interval, 0.55-0.88) lower risk than patients in the lowest persistence level (?12%). Conclusion: Our study demonstrated that persistent use of statins is associated with a lower overall cancer risk and particularly the risk of incident hematopoietic malignancies. In light of widespread statin consumption and increases in cancer incidence, the association between statins and cancer incidence may be relevant for cancer prevention.