Drug abuse is one of the public health problems in Nepal. Only limited research has been done to explore knowledge and sexual behaviors of injection drug users in Nepal. The objective of this research was to explore knowledge about human immunodeficiency virus (HIV) infection and sexual behavior among drug users in Nepal. More than 90% of participants had heard of HIV. Almost all participants who had heard of HIV knew that HIV is transmitted through unsafe sexual intercourse and through syringe use. In comparison to that, a small percentage of participants knew of infected blood and mother to child as modes of transmission of HIV. Injection drug users were less likely to use condoms during sexual intercourse with their wives. Awareness programs and behavior-change communication to alert drug users to the risks of sharing syringes need to be conducted, in addition to promoting the use of condoms during sexual intercourse with other women as well as with their wives.