BACKGROUND Topical retinoids in combination with antimicrobials have been proven to reduce acne lesions faster and to a greater degree than antimicrobial therapy alone . OBJECTIVE To compare the efficacy and safety of topical combination of 1% Nadifloxacin [NAD] and 0.025% Tretinoin [Tr] with 1% Clindamycin [CLN] and 0.025% Tr in patients of mild to moderate acne vulgaris of the face. METHODS There were two groups (40 patients in each group): Group A received (NAD+Tr) combination therapy and group B received (CLN+Tr) combination therapy. Efficacy was assessed by any reduction in the mean number of inflammatory lesions(IL), non-inflammatory lesions(NIL) and/or total lesions(TL) as well as by using Evaluator's Global Severity Scale (EGSS) of acne and safety was assessed by adverse effects of study medications at 0, 6 and at 12 weeks follow-up. RESULTS Both the study groups showed statistically significant intragroup reduction in NIL, IL and TL after 12 weeks of therapy. There was no statistically significant reduction at the end of 6 weeks of therapy in both the groups. At the end of 12 weeks of therapy there was a statistically significant reduction in IL, NIL and TL in group A. There was no statistically significant difference in the occurrence of adverse effects in both the groups. CONCLUSIONS Overall the study proved better efficacy of NAD+Tr compared to CLN+Tr. Medications of both the groups were safe and well tolerated.