Although randomized clinical trials have convincingly shown the efficacy of antihyperlipidemic drugs, both discontinuation of antihyperlipidemic drugs and failure to achieve goal lipid levels would be expected to attenuate the effect of these drugs on reducing the rates of hospitalization for coronary events. This study compares the rates of hospitalization and low-density lipoprotein cholesterol (LDL-C) levels during and after discontinuation of antihyperlipidemic drug therapy. A retrospective cohort study was conducted among 2369 patients at 2 health maintenance organizations (HMOs) during the period 1988 to 1994. Rates of coronary heart disease (CHD)-related hospitalization and non-CHD-related hospitalization and the LDL-C levels between 14 and 180 days after the initiation or discontinuation of drug therapy were compared for periods of antihyperlipidemic drug use and nonuse. The rate ratio for CHD hospitalization during periods of antihyperlipidemic drug use compared with periods of nonuse was 1.02 (95% CI, 0.74 to 1.40), excluding the first 6 months after initiation or discontinuation and controlling for patient sex, age, history of CHD, hypertension, diabetes, and HMO site. By contrast, the adjusted rate ratio was 0.70 (95% CI, 0.61 to 0.80) for non-CHD hospitalization. The percentage of patients with a history of CHD who achieved LDL-C levels <130 mg/dL was 27% < or =6 months after initiation of antihyperlipidemic drug therapy compared with 18% during gaps in drug therapy (P = 0.04). This study failed to demonstrate the effectiveness of lipid-lowering therapy in reducing CHD hospitalizations in community settings, apparently because most recipients either discontinued therapy or failed to achieve the desired LDL-C reduction while receiving therapy. These results indicate the need for interventions to improve patient compliance and management of lipid disorders.