Nicotinamide and clindamycin gels are two popular topical medications for acne vulgaris. This study aimed to compare efficacy of the topical 4% nicotinamide and 1% clindamycin gels in these patients. In this randomized, double-blind clinical trial, patients with moderate inflammatory facial acne vulgaris were randomly allocated to receive either topical 4% nicotinamide (n = 40) or 1% clindamycin gels (n = 40) twice daily. In each group, they were further categorized in two subgroups with oily and non-oily types of facial skin. The Cook's acne grade was determined at baseline and at weeks 4 and 8 post treatment. Acne grade decreased from an average of 5.93 ± 0.83 at baseline to 4.03 ± 1.33 at week 4 and 2.08 ± 1.59 at week 8 in nicotinamide receivers, and from an average of 5.70 ± 0.94 at baseline to 3.85 ± 1.66 at week 4 and 2.03 ± 1.53 at week 8 in the clindamycin group (within-group P < 0.001, between-group P > 0.05). Comparing with each other, nicotinamide and clindamycin gels were significantly more efficacious in oily and non-oily skin types, respectively. No major side effect was encountered by any patient. Skin type is a significant factor in choosing between topical nicotinamide and clindamycin in patients with acne vulgaris.