Background: Miltefosine is the only oral drug available for treatment of Indian Visceral Leishmaniasis (VL) which was shown to have an efficacy of 94% in a phase 3 trial in Indian subcontinent. Its unrestricted use has raised concern about its continued effectiveness. This study evaluates the efficacy and safety of miltefosine for the treatment of VL after a decade of use in India.MethodsIt was an open-label non-comparative study, in which 567 patients received oral Miltefosine (50 mg for those weighing /=25 kg, and 2.5 mg per kg for children <12years, daily for 28 days) in a directly observed manner. Patients were followed up for six months to see the response to therapy.ResultAt the end of treatment the initial cure rate was 97.5% (intention to treat) and at six month the final cure rate was 90.3%. Overall death rate was 0.9% (5/567) and two deaths were drug-toxicity related. Gastrointestinal intolerance was frequent (64.5%). The drug was interrupted in 9 (1.5%) patients due to the adverse events of the drug.ConclusionAs compared to the phase 3 trial which led to registration of the drug a decade ago, there is a substantial increase in the failure rate of oral miltefosine for treatment of VL in India.