A prospective study of risk factors associated with outbreaks of Newcastle disease (ND) in indigenous free-range chickens was carried out in three agro-ecological zones in eastern Uganda. Sixty households keeping chickens were randomly selected and studied from March 2004 to February 2005, covering rainy and dry seasons. Data on ND outbreaks, risk factors and flock dynamics were collected using an interviewer-administered questionnaire, while ND outbreaks were confirmed by haemagglutination inhibition test. Multivariate survival analyses were performed to identify the risk factors for Newcastle disease outbreaks. Although the survival time against ND was longer (> 100 days) in the dry compared to the rainy season, incidence in the two seasons was not significantly different (p > 0.05). None of the factors investigated was significantly associated with ND. However, purchasing of restocking chickens from the market and neighbourhood (hazard ratio [HR] = 1.79; 95% confidence interval [CI] 0.89-3.60), the presence of migratory wild birds (HR = 1.70; 95% CI 0.65-4.48) and being in agro-ecological zone 1 (HR = 1.48; 95% CI 0.66-3.36) showed a positive but non-significant association with risk for ND. To understand the roles of other domestic poultry species in the epidemiology of ND in rural free-range chickens, virus isolation and molecular characterization of isolates in addition to more prospective cohort studies with a larger sample size and similarly long period of follow-up are needed.