OBJECTIVES: To establish the effect of a pharmaceutical care program on compliance and persistence with once-daily atorvastatine treatment in patients with elevated cholesterol levels. METHODS: An open-label, prospective controlled trial of 1-year duration was conducted in Belgium, stratified by language region. A French speaking and a Flemish speaking region were randomized to a Measurement Guided Medication Management (MGMM) intervention consisting of review by the patients' pharmacist of the electronically compiled dosing history, a 'beep-card' that reminds patient of the dosing time and educational reminders. The control group received care as usual, also stratified between the 2 regions. Compliance was measured in all patients using the Medication Event Monitoring System (MEMS(r), AARDEX, Switzerland), defined as the % doses taken as prescribed (once-daily). Nonpersistence was defined as the % of patients who stopped using atorvastatine before the end of the study. Because of the skewed nature of compliance data, statistical reporting includes medians, 25-75% interquartile ranges, and non-parametric tests. RESULTS: A total of 393 patients were included: intervention group: n = 194, control group: n = 199. After 1 year follow-up and stratification by region, the median % of doses taken as prescribed (25% quartile - 75% quartile) was 96.1 (92.7-98.2) in the intervention group versus 89.9 (77.1-95.6) in the control group (p <0.0001). Other compliance variables showed similar results % prescribed doses taken: 98.9 (96.3-100.3) vs 95.2 (83.0-98.9), p <0.001, % doses within prescribed interval ± 25%: 92.8 (85.9-95.9) vs 84.4 (63.0-92.5), p <0.001 and Therapeutic Coverage: 96.1 (92.9-97.8) vs 93.6 (84.6-96.6), p <0.001. Persistence was significantly better in the intervention group: 87.1% vs 76.9% in the control group (p = 0.02). Explanatory analysis showed that the Flemish patient group and an elevated cardiovascular risk score were significantly related to better compliance and persistence. CONCLUSIONS: Measurement Guided Medication Management improved patient compliance and persistence with atorvastatine.