Immediate-release niacin manifests beneficial effects in cardiovascular disease with respect to dyslipidemic states. It lowers low-density lipoprotein (LDL) cholesterol, triglycerides, lipoprotein(a), and apoprotein B; at the same time, it increases high-density lipoprotein (HDL) cholesterol, HDL2, and apoprotein A-I. However, use of crystalline niacin has drawbacks: therapy requires multidose regimens, and side effects include flushing and pruritus. Slowing absorption with sustained-release formulations succeeds in decreasing flushing and increasing tolerance, but increases in hepatic enzyme levels have raised safety concerns. A new extended-release, once-daily formulation of niacin (Niaspan) shows promise in minimizing flushing while avoiding hepatotoxicity. A multicenter, randomized, double-blind clinical trial of Niaspan enrolled 122 patients with confirmed diagnosis of primary dyslipidemia (LDL cholesterol >4.14 mmol/L [160 mg/dL] and triglycerides <9 mmol/L [800 mg/dL]) into 3 treatment groups: (1) Niaspan 1,000 mg/day; (2) Niaspan 2,000 mg/day; and (3) placebo. The primary treatment endpoint was LDL-cholesterol level. This endpoint was not significantly affected by placebo (0.2% increase), but Niaspan decreased LDL cholesterol by 5.8% (1,000 mg/day) and 14.6% (2,000 mg/day) (p <0.001). Likewise, with placebo there were significant changes in total cholesterol, triglycerides, lipoprotein(a), and apoprotein B, whereas both Niaspan 1,000 and 2,000 mg/day significantly (p <0.001) decreased these parameters. In addition, both Niaspan groups showed significant (p <0.001) increases in HDL cholesterol (17% and 23%, respectively), including HDL subfractions. With respect to flushing, 20% of the placebo group reported at least 1 episode, whereas 88% and 83% of the Niaspon 1,000- and 2,000-mg/day groups, respectively, reported episodes. There was no hepatotoxicity as liver enzyme levels remained within clinically accepted limits in all treatment groups. However, Niaspan 2,000 mg/day showed a significant increase in aspartate aminotransferase compared with baseline and placebo. This trial demonstrated a cholesterol-modifying effect of Niaspan consistent with those reported for niacin, but demonstrated a better tolerance for flushing. Moreover, in contrast to sustained-release formulations, Niaspan showed relatively mild hepatic effects.