Aerosolized pentamidine is Food and Drug Administration approved to treat Pneumocystis pneumonia via a route that does not lead to systemic absorption or toxicity. Because Leishmania is also susceptible to pentamidine and mucosal leishmaniasis is also an infection of the respiratory tract, we performed a pilot study of aerosolized pentamidine (300 mg for 10 days over approximately 4 weeks) for mucosal leishmaniasis caused by Bolivian Leishmania braziliensis with a 2-year follow-up. Of 15 patients, 6 of 7 patients with initially mild disease were cured, 3 of 4 patients with initially moderate disease relapsed at the 18- to 24-month follow-up visits, and 3 of 4 patients with initially severe disease failed early after treatment. This study suggests that inhaled pentamidine may be useful as a well-tolerated treatment of mild mucosal leishmaniasis and that to rule out relapse, mucosal leishmaniasis follow-up should extend to 2 years.