Topical antibiotics are the mainstay of therapy in mild to moderate inflammatory acne. Topical erythromycin is one of the most common prescribed topical antibiotics. Nadifloxacin, another topical antibiotic for acne, was recently introduced into the market in our country. In this study, we compared the efficacies and safety of topical nadifloxacin 1% cream and erythromycin 4% gel in acne. A total of 86 patients with mild to moderate facial acne were randomized into two treatment groups. The efficacies of the drugs were assessed by lesion counts. An acne severity index (ASI) was also calculated. In both groups, there was a significant reduction in lesion counts and ASI scores beginning from the first visit at week 4. This reduction continued throughout the 12-week study period. Both treatments were well tolerated. We conclude that when topically applied, both nadifloxacin 1% cream and erythromycin 4% gel are equally effective and safe treatments for mild to moderate facial acne.