Background: Cutaneous leishmaniasis (CL) is an endemic disease in Iraq, now is running in an outbreaks. Many therapies have been tried in treatment of the disease. Objective: Loranthus europaeus (LE) is a well-known medical plant and has many pharmacological effects in many in vitro studies. The aim of the study is to evaluate the effectiveness of 40% LE ointment and compared it with topical 25% podophyllin solution in treatment of acute CL. Patients and Methods: Thirty five patients with acute CL were enrolled in this single blinded, therapeutic, comparative study, which was done in the Department of Dermatology, Baghdad Teaching Hospital, Baghdad, Iraq during January 2015-Jully 2015. The total number of lesions were 86 (76 lesions treated and ten lesions in a covered area left without treatment as control). Duration of lesions ranged from 4 to 12 (7.37 ± 2.77) weeks. The size of lesions ranged from 0.5 -7 (2.81 ± 1.76) cm. Diagnosis was confirmed by biopsy and/or smears. Lesions were divided in to two groups and scored as (mild, moderate, marked, complete cure) according to a modified Sharquie's leishmania score to assess the objective response to the topical or systemic therapy. Group A: Thirty three (43.42%) lesions treated with topical 25% podophyllin solution once weekly for maximum 6 weeks. Group B: Forty three (56.58%) lesions treated with 40% LE ointment once daily at bedtime for 6 hours under occlusion for maximum 6 weeks. The followed-up was carried out every 2 weeks for 8 weeks during treatment, then monthly for next three months after end of therapy. Results: the total number of lesions was 86 lesions, 46 (53.49%) were ulcerated and 40 (46.51%) were dry; 18 (51.43%) patients had single lesion while 17 (48.57%) patients had multiple lesions. At the end of therapy (6 weeks after starting treatment), the cure rate was 84.84% in Group A, and 79.07% in Group B. When the two groups compared with each other there was no statistical significance difference were P value = 0.648. While untreated ten lesions that lefts as control did not showed any signs of healing. Conclusion: Topical 40% Loranthus europaeus ointment is a new effective modality for treatment of acute CL and as effective as 25% podophyllin solution with no any noticeable local or systemic side effects.