Topical retinoid and antibiotic combination therapy is an integral part of acne treatment and is considered the appropriate first-line therapy according to the Japanese guideline for moderate and severe acne. In this combination, clindamycin or doxycycline are mostly used as antibiotics, but there have been no reports on the effectiveness of nadifloxacin, a widely used antibiotic in Japan and European countries for acne, in combination with topical retinoid. To confirm the efficacy and safety of adapalene gel and nadifloxacin cream in the treatment of Japanese patients with acne vulgaris, a total of 50 patients were randomized to the two groups, the combination therapy and the adapalene monotherapy, and each therapy was tested for 8 weeks. The percentage reduction in the number of inflammatory acne lesions was evaluated and the safety was monitored through adverse events. The combination of adapalene gel and nadifloxacin cream produced a significantly higher reduction in the inflammatory lesions at 2 weeks (P= 0.047) and at 8 weeks (P= 0.011) after the starting than did adapalene gel monotherapy. The combination did not elevate the side effects of erythema and scale scores, but rather significantly depressed erythema at 1 week. This study showed the efficacy and safety of the combination therapy of nadifloxacin cream with adapalene gel for the inflammatory acne.