Drug-related factors and parasite resistance have been implicated in the failure of pentavalent antimonials (Sb(v)) in the Indian subcontinent; however, little information is available on host-related factors. Parasitologically confirmed kala-azar patients, treatment naïve to Sb(v), were prospectively recruited at a referral hospital in Nepal and were treated under supervision with 30 doses of quality-assured sodium stibogluconate (SSG) 20mg/kg/day and followed for 12 months to assess cure. Analysis of risk factors for treatment failure was assessed in those receiving >or=25 doses and completing 12 months of follow-up. One hundred and ninety-eight cases were treated with SSG and the overall cure rate was 77.3% (153/198). Of the 181 cases who received >or=25 doses, 12-month follow-up data were obtained in 169, comprising 153 patients (90.5%) with definite cure and 16 (9.5%) treatment failures. In the final logistic regression model, increased failure to SSG was significantly associated with fever for >or=12 weeks [odds ratio (OR)=7.4], living in districts bordering the high SSG resistance zone in Bihar (OR=6.1), interruption of treatment (OR=4.3) and ambulatory treatment (OR=10.2). Early diagnosis and supervised treatment is of paramount importance to prevent treatment failures within the control programme.