Diaper dermatitis (DD) complicated by candidiasis is a common problem in diaper-wearing infants and children. We report a double-blind, vehicle-controlled, parallel-group study evaluating the efficacy and safety of a low concentration of miconazole nitrate in a zinc oxide/petrolatum ointment for the treatment of DD complicated by candidiasis. Patients (N=330) who had DD with a severity score of 3 or higher were enrolled. Those patients with a baseline potassium hydroxide (KOH) preparation and a baseline culture specimen that both tested positive for Candida were retained for efficacy analysis (n=236). Miconazole nitrate 0.25% ointment or a zinc oxide/petrolatum vehicle control were applied to all clinically affected areas of patients with DD for 7 days at each diaper change and after bathing. A follow-up test-of-cure visit was conducted at day 14. Among the patients completing the study, the overall rate of cure (clinical cure plus microbiologic cure) was 23% for the miconazole nitrate group and 10% for the vehicle control group (P=.005); the rate of clinical cure (complete rash clearance, DD severity score=0 at day 14) was 38% for the miconazole nitrate group and 11% for the vehicle control group (P<.001); and the rate of microbiologic cure (no culture growth of Candida) was 50% for the miconazole nitrate group and 23% for the vehicle control group. The vehicle control resulted in mild improvement at day 3 but little or no subsequent improvement. The discontinuation rate due to clinical failure was substantially lower for the miconazole nitrate group (4%) than the vehicle control group (47%). The mean DD severity index score for the miconazole nitrate group was significantly lower from day 3 through day 14 compared with that of the vehicle control group (P<.001). Adverse events were assessed as either unlikely to be related to study medication or unrelated to study medication. By including only those patients with microbiologically confirmed Candida infection, the study population may not be fully indicative of patients treated for DD in routine clinical practice. Our data show that miconazole nitrate 0.25% ointment was well tolerated and significantly more effective than the zinc oxide/petrolatum vehicle control for treatment of DD complicated by candidiasis.