Background: Because of limited work opportunities in Nepal and the open-border provision between Nepal and India, a seasonal labor migration of males from Far-Western Nepal to India is common. Unsafe sexual activities of these migrants in India, such as frequent visits to brothels, lead to a high HIV prevalence among them and to a potential transmission upon their return home to Nepal. The present study aims to evaluate the role of such seasonal labor-migration to India on HIV transmission in Far-Western Nepal and to assess prevention programs. Methods: An HIV epidemic model was developed for a population in Far-Western Nepal. The model was fitted to the data to estimate the back and forth mobility rates of labor-migrants to India, the HIV prevalence among migrants and the HIV transmission rate in Far-Western Nepal. HIV prevalence, new infections, disease deaths and HIV infections recruited from India were calculated. Prevention programs targeting the general population and the migrants were evaluated. Results: Without any intervention programs, Far-Western Nepal will have about 7,000 HIV infected individuals returning from India by 2015, and 12,000 labor-migrants living with HIV in India. An increase of condom use among the general population from 39% to 80% will reduce new HIV infections due to sexual activity in Far Western Nepal from 239 to 77. However, such a program loses its effectiveness due to the recruitment of HIV infections via returning migrants from India. The reduction of prevalence among migrants from 2.2% to 1.1% can bring general prevalence down to 0.4% with only 3,500 recruitments of HIV infections from India. Conclusion: Recruitment of HIV infections from India via seasonal labor-migrants is the key factor contributing to the HIV epidemic in Far-Western Nepal. Prevention programs focused on the general population are ineffective. Our finding highlights the urgency of developing prevention programs which reduce the prevalence of HIV among migrants for a successful control of the HIV epidemic in Far-Western Nepal.