Background: Seborrheic dermatitis is one of the most common skin diseases. Objective: The purpose of this study was to compare the topical and oral ketoconazole in treatment of intractable cases of seborrheic dermatitis referring to Faghihi Hospital in Shiraz. Patients and Methods: This study was performed on 80 cases of intractable seborrheic dermatitis in 1376-1378. The patients were randomized in two treatment groups. Group included 40 patients who were treated with topical ketoconazole cream 2% two times per day for 4 weeks, and group 2 included 40 patients who received oral ketoconazole 200 mg daily for 4 weeks. Results: Topical ketoconazole clinically cured 35 (87.5%) and oral ketoconazole cured 38 (95%) of patients. This difference was not statistically significant. However topical ketoconazole was accompanied with a lower frequency of side effects than the systemic form. Conclusion: Both topical and oral ketoconazole can be regarded as a highly effective and safe treatment for seborrheic dermatitis.