Some patients with initial normal levels of high-density lipoprotein cholesterol (HDL-C) have lower HDL-C levels during lipid-lowering treatment. The aim of this study was to estimate the prevalence of low HDL-C (< 1.0 mmol/L; < 40 mg/dL) before and during lipid-lowering treatment. Additionally, the prevalence of low HDL-C during fibrate and statin treatment was compared. All patients attending two Health Insurance Associations during February and March 2002 for continuing reimbursement of their lipid-lowering drug were included in this study. Date of birth, sex and the actual lipid-lowering drug were recorded. The most recent lipoprotein levels and those after a three-month diet before the start of the treatment were recorded. In total, 2,259 patients (56% women) were included; 69% were treated with statins and 31% with fibrates. Low HDL-C levels were found before the initiation of the treatment in 7% of the statin patients and in 11% of the fibrate patients. During treatment, 10% of the statin patients and 13% of the fibrate patients had low HDL-C levels. The proportion of patients whose HDL-C decreased below 1.0 mmol/L (40 mg/dL) during treatment was 6% for statins and 4% for fibrates. Although lipid-lowering drugs are known to increase HDL-C levels slightly, not all patients benefit from this effect.