The efficacy and safety of oral moxifloxacin (400 mg once daily, 7 days) versus cephalexin (500 mg three times daily, 7 days) were compared in a prospective, multicentre, randomised, double-blind trial in 401 adults with uncomplicated skin infections. Clinical outcome was evaluated in 351 patients. Moxifloxacin proved to be as effective as cephalexin both clinically (90% versus 91%, respectively) and bacteriologically in eradicating the most frequently isolated pathogen Staphylococcus aureus (92% and 93%, respectively). Moxifloxacin was more effective than cephalexin in eliminating Streptococcus spp. (90% and 82%, respectively). Drug-related adverse events were comparable in both treatment groups with the most frequently reported being nausea in the moxifloxacin-treated patients and headache in the cephalexin-treated patients. Medication was discontinued due to unwanted reactions in 3% of the moxifloxacin- and 4% of the cephalexin-treated patients. Moxifloxacin, 400 mg once daily for 7 days, is as safe and effective as cephalexin 500 mg three times daily for 7 days in the treatment of uncomplicated skin infections.