The objectives of the study were to analyze 1) compliance with an HMG-CoA reductase inhibitor, 2) the relationship between treatment compliance and sociodemographic, clinical, and psychological criteria, and 3) the effect of raising patients' awareness through distribution of an information notice. The results analyzed in this article compare the noncompliant and compliant population independently of awareness. This open-label study was conducted in two randomized parallel groups: a control group that received the information normally given by the practitioners, and an awareness group that received specific informational brochures on diet and cardiovascular risk factors and the reasons for the treatment. Male and female patients (n = 3845) aged 18 to 75 years with primary hypercholesterolemia (type IIa and IIb), not taking a cholesterol-lowering drug or for whom an ongoing treatment was poorly tolerated or ineffective, were to be included. Cholesterol levels had to be greater than 250 mg/dL (or 200 mg/dL if previous coronary history) and triglyceride levels less than 350 mg/dL. A total of 2888 subjects (75%) were defined as compliant (taking more than 90% of the prescription) and 957 (25%) noncompliant. Both populations are identical for age, sex ratio, and different risk factors, with the exception of diabetes. The adverse effects in noncompliant subjects were very clearly different, with an overrepresentation of gastrointestinal and neurologic effects and the noncompliant patients more frequently having more than one adverse effect. Noncompliant patients had an identical duration of follow-up, and the number of patients claiming to have a symptom related to hypercholesterolemia, self-evaluation of cardiovascular risk level, and source of knowledge about cholesterol and diet was similar in both groups. In contrast, in the noncompliant group, there were a larger number of symptomatic patients who thought the drug did not improve the symptoms. In practice, these results show that physicians should systematically evaluate compliance by looking for and analyzing adverse effects and by reassuring the patient when these effects are minor or probably unrelated to the treatment. Diabetics and polymedicated patients deserve special attention in this regard.