We performed a multicenter double-blind clinical trial to compare cefditoren pivoxil (CDTR-PI), a new oral cephem antibiotic, with cefaclor (CCL) in the treatment of skin and skin structure infections (furuncle, furunculosis, carbuncle, cellulitis, erysipelas, lymphangitis and lymphadenitis). CDTR-PI was given orally in a dose of 200 mg three times a day, and CCL in a dose of 250 mg three times a day. One hundred fifty-nine patients were randomly assigned to receive either CDTR-PI (83 patients) or CCL (76 patients). One hundred fourty-five of these patients (CDTRPI, 73; CCL, 72) were evaluated in terms of efficacy, 150 (CDTR-PI, 77; CCL, 73) in terms of overall safety, and 147 (CDTR-PI, 75; CCL, 72) in terms of clinical usefulness. 1. No significant differences were detected in the efficacy rates between the two drug groups. The overall efficacy rate was 97.3% (71/73) for the CDTR-PI group and 90.3% (65/72) for the CCL group. 2. The global improvement rate after 5 days of treatment was 92.4% (61/66) for the CDTR-PI group and 84.8% (56/66) for the CCL group, with no significant difference between the two drug groups. 3. The safety rate was 87.0% (67/77) for the CDTR-PI group and 93.2% (68/73) for the CCL group, with no significant difference between the two drug groups. 4. The clinical usefulness rate was 90.7% (68/75) for the CDTR-PI group and 88.9% (64/72) for the CCL group, with no significant difference between the two drug groups. 5. The bacteriological response rate was 90.0% (36/40) for the CDTR-PI group and 91.2% (31/34) for the CCL group, with no significant difference between the two drug groups. 6. The side effect incidence was 11.7% (9/77) for the CDTR-PI group and 2.7% (2/73) for the CCL group, with no significant difference between the two drug groups. Abnormal laboratory values were noted in 2 patients in the CDTR-PI group and in 4 patients in the CCL group, with no significant difference between the two drug groups. We conclude that CDTR-PI is as effective, safe and useful as CCL in the treatment of skin and skin structure infections.