Background: There are many topical therapies for the treatment of plaque psoriasis like steroid, dithranol, tar and vitamin D analogues, but none of them is ideal. Most recently, in a pilot study, podophyllin 5% ointment on every other day regimen was as effective as clobetasole 0.05% ointment twice daily. Objective: To reassess the efficacy of a higher concentration of podophyllin (10%) in the treatment of mild psoriasis in comparison with clobetasole using a different regimen. Patients and Methods: This is therapeutic, comparative, placebo-controlled study conducted at the Department of Dermatology-Baghdad Teaching Hospital, during the period of January 2011 - October 2012. Eighty-seven patients with mild plaque-type psoriasis were divided into three groups: Group A (30) patients were treated with podophyllin 10% ointment; Group B (30) patients were treated with clobetasol propionate 0.05% ointment and Group C (27) patients were treated with Vaseline as a placebo control group. All patients were treated on every other day. The efficacy was evaluated every 2 weeks for 8 weeks using PASI score and the local and systemic side effects were recorded. The relapse was recorded after cessation of therapy in those patients who achieved good response during another 8 weeks follow-up period. Results: The patients were 60 (68.9%) males and 27 (31.1%) females (male: female ratio, 2.2:1). Their ages ranged from 18 - 62 (36.4 ± 10) years. Their disease duration ranged from 0.1 - 40 (7.8 ± 8.5) years. Their baseline PASI score ranged from 1.6 - 9.6 (4.4 ± 5.85). At the end of 8th week of therapy, Group A patients had achieved much higher reduction in PASI score (77.4 ± 14.1) than Group B patients (60.4 ± 27.8), P value = 0.004, and both of them were with statistically and significantly higher PASI reduction than patients in Group C (28 ± 23.4), P value = <0.001. The total relapse rate during 8 weeks follow-up was much lower among Group A treated patients, 20% versus 66.6% in Group B (P-value = 0.002), while the relapse rate was 100% in the Group C patients. Regarding side effects: 3 (10%) patients developed erythema, burning, pain, blistering and hypopigmentationin Group A. No side effects were reported in Groups B nor C patients with no statistically significant difference among the three groups (P = 0.052). Conclusion: Podophyllin 10% ointment was more effective than clobetasole 0.05% ointment on every other day treatment regimen at the end of 8 weeks treatment with no side effects and a much lower relapse rate in treatment of mild plaque-type psoriasis.