Introduction Acne patients are frequently associated with abnormal lipid profile. It may be useful to apply high dose of niacin that regulates the lipid profile along with acne treatment. There is no report about high dose of niacin in treatment of acne. Objective To evaluate the therapeutic effect and safety of high-dose niacin in acne vulgaris. Methods Acne patients were randomly allocated to two treatment groups. Both groups were treated orally with the tablets for 12 weeks; the niacin group at an increasing dose of niacin tablet: 2000 mg (40 mg/kg/d). The control group (nicotinamide group) at a dose of nicotinamide tablet: 600 mg (10 mg/kg/d). All patients were asked not to consume certain foods such as milk and alcohol. A high-protein, low-fat and low-glycemic-load diet was recommended in both groups. Results A total of 108 patients were finished the study. Niacin group: 56 patients; control group: 52 patients. After 12 weeks of treatment, niacin and nicotinamide caused improvement in acne patients. Percentage Improvement in the niacin group (82.37±7.837) %was significantly higher than in the nicotinamide group (63.19±10.18)%, P<0.01. The number of successful cases in the niacin group was significantly higher than in the nicotinamide group after 12 weeks of treatment, (χ2 = 10.55, P<0.01). Conclusions High dose niacin can really do it work in treatment of acne vulgaris. The therapeutic effcct of High dose of niacin in treatment of acne vulgaris is more effective than nicotinamide.