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Therapeutic failure in the treatment of cutaneous leishmaniasis (CL) occurs in 5% of patients infected by Leishmania braziliensis. This study evaluates the use of topically applied granulocyte macrophage colony-stimulating factor (GM-CSF) combined with the standard dose of antimony to treat refractory cases of CL. Five patients who had received three courses or more of antimony were enrolled in an open-label clinical trial. One to 2 mL of the GM-CSF solution (10 μg/mL in 0.9% saline) was reapplied topically, and dressings were changed three times per week for 3 weeks, associated with standard parenteral antimony (20 mg kg−1 day−1 for 20 days). All the patients healed their CL ulcers; 3 healed within 50 days (21, 27, and 44 days) and 2 in 118 and 120 days after beginning therapy. There were no side effects. This study shows that combined topically applied GM-CSF and antimony can be effective and well tolerated in the treatment of relapsed CL.