Abstract INTRODUCTION: Different studies have demonstrated that low levels of high-density lipoprotein (HDL) cholesterol in serum are significantly related to the progression of coronary artery disease (CAD) and its related mortality. This study was performed primarily to assess the effectiveness of supplementing treatment with statins with low-dose (100 mg, bid) fast-release nicotinic acid (the only form of this drug produced in Iran) in increasing HDL; we also aimed to evaluate the effect of this regimen on other lipoproteins, and to investigate any possible side effects. methods: This double-blind placebo-controlled randomized clinical trial was conducted on patients who were treated with simvastatin (20 mg/daily) for at least four weeks and did not receive any other lipid-lowering medications. The patients were divided into two groups of 50. The case group was treated with niacin tablets (100 mg, bid) and simvastatin (20 mg/daily). The control group was treated with placebo tablets (bid) and simvastatin (20 mg/daily). All patients underwent two 6-week crossover periods and a 2-week washout period. Liver-function biomarkers (ALK-P, SGPT, SGOT), serum lipids, uric acid, CPK and fasting blood sugar (FBS) were measured before and after each course of treatment. Data were analyzed with chi-square test and paired t-test. results: Serum HDL increased from 42.44±8.5 to 44.01±8.39 mg/dl in the case group, with a mean increase of 2.56 mg/dl (P<0.05). HDL decreased from 41.5±9.1 to 40.9±9.4 mg/dl in the control group (P>0.05). Mean serum HDL was significantly different between the case and control groups (P<0.05). The increase in mean total cholesterol and low-density lipoprotein (LDL) cholesterol in the control group, and the decrease in triglyceride (TG) in both groups were not statistically significant (P>0.05). In follow-up, flushing was reported in 44.4% of case patients, resulting in discontinuation of treatment in 38.5% of patients. Flushing was reported in 5.6% of controls, resulting in discontinuation of treatment in 20% of patients. Muscle pain was reported in 24.4% of the case patients, resulting in discontinuation of treatment in 47.6% of the patients. Only 3.3% of the controls reported muscle pain, which led to discontinuation of treatment by the physician in 66.7% of the patients. CONCLUSIONS: Low-dose fast-release niacin led to significant HDL increase; hence we recommend that treatment of dyslipidemic patients with statins be supplemented with low-dose niacin, which is available in Iran. Keywords: Niacin, simvastatin, lipoprotein.