Lactoferrin is an iron-binding milk-derived protein that has shown antibacterial and anti-inflammatory effects in vitro and in vivo. The objective of this study was to determine the efficacy and safety of lactoferrin, combined with vitamin E and zinc, for mild to moderate acne vulgaris. In this randomized, double-blind, placebo-controlled trial, 168 subjects aged 13-40 years old were randomly assigned to take either a capsule formulation containing lactoferrin with vitamin E and zinc or placebo twice a day for 3 months. The primary outcome measure was a reduction in the number of acne lesions compared to placebo. A total of 164 subjects completed the study per protocol. The lactoferrin group (n = 82) showed a significant median percent reduction in total lesions as early as 2 weeks (14.5%, P = 0.0120), with the maximum reduction occurring at week 10 (28.5%, P < 0.0001) compared to placebo group (n = 82). Maximum reduction in comedones (32.5%, P < 0.0001) and inflammatory lesions (44%, P < 0.0001) was also seen at week 10 compared to placebo. Sebum scores were improved by week 12. No adverse events were observed during the trial. A twice daily regimen of lactoferrin with vitamin E and zinc significantly reduced acne lesions in people with mild to moderate acne vulgaris.