Although the beneficial effect of statins in secondary prevention of cardiac events is well established, their effectiveness in primary prevention is questionable when most evidence derives from randomized controlled trials and not "real-life" data. To evaluate the association between persistent use of statins and risk of acute nonfatal cardiovascular events in primary prevention patients in community settings, we retrospectively analyzed a cohort of 171,535 adults 45 to 75 years old with no indication of cardiovascular disease who began statin therapy from 1998 to 2009 in a large health maintenance organization in Israel. Persistence with statins was measured by the proportion of days covered with dispensed prescriptions of statins during the follow-up period. Main outcome measurements were occurrence of myocardial infarction or performance of a cardiac revascularization procedure. Incidence of acute cardiovascular events during the follow-up period (993,519 person-years) was 10.22 per 1,000 person-years. Persistence with statins was associated with a lower risk of incident cardiac events (p for trend <0.01). The most persistent users (covered with statins for <80% of their follow-up time) had a hazard ratio of 0.58 (95% confidence interval 0.55 to 0.62) compared to nonpersistent users (proportion of days covered <20%). Similar results were found when analyses were limited to patients with >5 years of follow-up. Treatment with high efficacy statins was associated with a lower risk of cardiac events. In conclusion, our large and unselected community-based study supports the results of randomized controlled trials regarding the beneficial effect of statins in the primary prevention of acute cardiac events.