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Effective therapy for chronic illness requires daily medication adherence (DMA) for prolonged periods. Overall medical regimen complexity may represent one barrier to successful adherence.To assess the relationship between the number of concurrently prescribed medicines and adherence to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), we analyzed a cohort of 5488 patients in a single health insurance plan who began statin therapy between July 1, 1999, and June 30, 2002. We assessed 2 parameters of statin adherence: (1) DMA ([total number of pills dispensed/total number of days between first and last prescription] ×100) and (2) refill persistence (RP) (consecutive months of refills after initial prescription).The cohort was 61.6% male, with a mean ± SD age of 52.7 ± 9.3 years. Patients were prescribed a mean ± SD of 2.9 ± 2 total medicines (range, 1–13), with a mean ± SD statin DMA of 82.1% ± 26.5%. By 12 months, only 68% of patients continued filling statin prescriptions. After controlling for age, income level, and treatment for hypertension or ischemic heart disease, a greater number of concurrently prescribed medicines was significantly associated with better DMA (P = .005) and longer RP (P = .03).In this cohort, statin DMA was generally adequate, but RP was suboptimal. Patients with more concurrently prescribed medicines had higher DMA and better RP, even after adjusting for demographic factors and cardiovascular comorbidity. Physicians should not be deterred from initiating statin therapy by a patient's medical regimen complexity but should be alert for lack of therapy persistence, particularly in younger and healthier patients.