Objective: Adherence to statin therapy is insufficient in patients with hypercholesterolemia. The objective of the study was to assess the effect of an adherence programme on cardiovascular events. Methods: In the ORBITAL (Open-label primary care study: Rosuvastatin-Based compliance Initiatives linked To Achievement of LDL goals) Study, patients were included with an indication for statin therapy according to the Joint European Guidelines. Patients were enrolled consecutively in 1961 primary care practices. The adherence programme included health education material and telephone calls in regular intervals. Cardiovascular events were defined as myocardial infarction, stroke, or revascularisation during the 3-year follow-up. Health-related quality of life was assessed with the visual analogue scale (VAS). Results: A total of 7640 patients were included, with 6.4% having at least one cardiovascular event. There was no significant difference in events between intervention and control group (relative risk [RR] 1.1, 95% confidence interval [CI] 0.9–1.3). After adjustment for age, sex and baseline cardiovascular risk, risk of event was significantly and inversely associated with VAS score (RR per unit increase 0.99; 95% CI 0.98–0.99) and smoking status (never vs. yes) (RR 0.73; 95% CI 0.53–0.98). Conclusion: The adherence programme did not have an effect on cardiovascular events in patients with hypercholesterolemia. The importance of smoking prevention needs to be emphasized. ClinicalTrials.gov Identifier: NCT00379249