Background. Extended release (ER)-niacin therapy, which has been associated with reduced glucose tolerance in human immunodeficiency virus (HIV)-seronegative individuals, has not been evaluated in the HIV-infected population. Methods. This open, prospective trial evaluated the safety and efficacy of ER-niacin therapy for antiretroviral therapy-associated dyslipidemia. Fourteen individuals received ER-niacin at maximum doses of 2000 mg per day for 14 weeks. Results. Significant reductions in serum levels of triglycerides (P = .02), total cholesterol (P = .005), and non-HDL cholesterol (P = .04) were seen after ER-niacin therapy. Seven of 11 subjects were glucose intolerant after ER-niacin therapy; for 3 of these subjects, this was a new finding. β-Cell sensitivity to basal glucose levels increased significantly without concomitant increase in overall glucose disposition indices. The values for the homeostasis model of insulin resistance index increased significantly (P = .005). Conclusion. ER-niacin's role in the treatment of antiretroviral therapy-associated dyslipidemia requires further evaluation, but the results of this pilot study indicate that it is safe and tolerated and provides a valuable treatment option.