The object of this open-label, randomized, comparative study was to evaluate the efficacy and safety of fleroxacin versus conventional therapy (cefazolin plus gentamicin/cephalexin) in the treatment of patients with bacterial liver abscess. Thirty-one adult patients (26 men and 5 women) received fleroxacin 400 mg orally once daily for 3 weeks, and 30 adult patients (21 men and 9 women) received conventional therapy for 3 to 4 weeks. Patients was assessed on day 3 of treatment, thereafter every week during treatment, and at 7 to 14 days (compulsory follow-up) after treatment for assessment of bacteriologic, clinical, and safety parameters. A total of 20 patients in the fleroxacin group and 22 patients in the conventional therapy group were evaluated. Klebsiella pneumoniae was the predominant pathogen isolated in all evaluable cases. Bacteriologic cure was achieved in 14 (70%) of 20 patients on fleroxacin therapy compared with 18 (81.8%) of 22 patients on conventional therapy (p=0.48). Clinical cure was achieved in 12 (60%) and 18 (81.8%) patients, and improvement in 2 (10%) and 1 (4.5%) patients in the fleroxacin and conventional therapy group, respectively. Most of adverse effects were of mild intensity. Oral fleroxacin once-daily administration is an effective, alternative treatment of bacterial liver abscess.