This study compared the efficacy and safety of lomefloxacin with that of trimethoprim/sulfamethoxazole (TMP/SMX) in the treatment of adult patients with acute diarrhea of bacterial etiology. Two centers enrolled a total of 133 patients; 99 (74%) presented with severe symptoms. The patients were randomized to receive either lomefloxacin 400 mg once daily (n=68) or TMP/SMX 160/800 mg twice daily (n=65) for five days. Bacteriologic success was achieved in 89.5% of evaluation lomefloxacin-treated patients and in 97.5% of patients treated with TMP/SMX. Clinical success was achieved in 100% and 97.5% of patients in the two treatment groups, respectively. The predominant organisms isolated in both groups at baseline, i.e. Shigella flexneri, Vibrio parahaemolyticus, and Salmonella Group D, were eradicated in all patients. Campylobacter jejuni was isolated at baseline in four patients in the lomefloxacin group but in none randomized to receive TMP/SMX; this organism persisted in three patients. Adverse events were experienced by 14 (23%) of the lomefloxacin-treated patients and by 18 (30%) of the TMP/SMX-treated patients. All adverse events reported were mild or moderate in severity and their distribution was similar in both groups. The results of this study show that lomefloxacin 400 mg once daily is as effective as TMP/SMX 160/800 mg twice daily and suggest that lomefloxacin is a promising new quinolone for the treatment of bacterial diarrhea. © 1992.