Background: In addition to tetracyclines, zinc may constitute an alternative treatment in inflammatory lesions of acne. Objective: To evaluate the place of zinc gluconate in relation to antibiotics in the treatment of acne vulgaris. Methods: Zinc was compared to minocycline in a multicenter randomized double-blind trial. 332 patients received either 30 mg elemental zinc or 100 mg minocycline over 3 months. The primary endpoint was defined as the percentage of the clinical success rate on day 90 (i.e. more than 2/3 decrease in inflammatory lesions, i.e. papules and pustules). Results: This clinical success rate was 31.2% for zinc and 63.4% for minocycline. Minocycline nevertheless showed a 9% superiority in action at 1 month and one of 17% at 3 months, with respect to the mean change in lesion count. Regarding safety, the majority of the adverse effects of zinc gluconate and of minocycline concerned the gastrointestinal system and weremoderate (5 dropouts with zinc gluconate and 4 with minocycline). Conclusion: Minocycline and zinc gluconate are both effective in the treatment of inflammatory acne, but minocycline has a superior effect evaluated to be 17% in our study.