This study compares immigrant (i.e., foreigner) with non-immigrant (i.e., local/native) HIV-related risk behaviors among female sex workers (FSW) in South America. A total of 1,845 FSW were enrolled in Argentina, Bolivia, Ecuador, and Uruguay. According to their nationality, 10.1% of participants were immigrant FSW. Immigrant FSW were more likely to be younger in Argentina; to work in a disco/bar in Bolivia; to be single and use illegal drugs in Ecuador; and to work in a brothel, consume alcohol, and have sex with foreign clients in Uruguay. HIV-related sexual and drug use behaviors were more common among immigrant FSW in Bolivia, Ecuador, and Uruguay. Country-specific HIV/STI prevention and control programs should be developed for immigrant FSW populations in South America.