This post hoc analysis from the Coronary Drug Project (CDP) evaluated the effects of niacin monotherapy on clinical outcomes in patients with and without the metabolic syndrome (MS). The CDP was a randomized, placebo-controlled clinical trial of lipid-modifying agents in men with previous myocardial infarction (MI). Of the 5 drug regimens, only niacin significantly decreased definite recurrent nonfatal MI at 6 years and total mortality at a 15-year follow-up. Patients treated with niacin (n = 1,119) and placebo (n = 2,787) were grouped according to the presence or absence of the MS at baseline. The MS was defined on the basis of meeting > or =3 of 5 criteria from the current National Cholesterol Education Program guidelines in a small subgroup of patients with high-density lipoprotein cholesterol determinations at baseline and on the basis of > or =3 of 4 criteria in the total population, excluding the high-density lipoprotein cholesterol criterion. Niacin decreased the occurrence of 6-year MI and 15-year total mortality similarly among patients with or without the MS. For example, in the total population, 15-year total mortality rates were 60% and 64% (hazard ratio 0.86) in patients with the MS treated with niacin and placebo, respectively, and 50% and 57% (hazard ratio 0.86) in those without the MS (Z for interaction = 0.06, indicating homogeneity of the treatment effect across groups). In conclusion, these results support the use of niacin in postinfarction patients with and without the MS.