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More than 200 female sex workers (FSWs) participating in commercial sex along the Highlands Highway of Papua New Guinea were identified in a previous survey. This has implications for the spread of sexually transmitted infections (STIs) and human immunodeficiency virus (HIV) to areas and population groups serviced by the road.The goal of this study was to estimate the prevalence of gonorrhea, chlamydia, syphilis, trichomoniasis, and HIV among FSWs in Goroka and Kainantu in the Eastern Highlands Province (EHP) and to identify correlates that could be considered in intervention and control.Self-identified FSWs recruited through the Goroka Sex Workers Peer-Mediated Programme were invited to participate. All consenting FSWs underwent pretest counseling and provided sociodemographic and behavioral data using a structured questionnaire. The women were also asked to self-collect vaginal specimens and to provide peripheral blood to detect the respective STIs and HIV.Results were available for 211 FSWs. None of the women were positive for HIV. The overall estimated rates for gonorrhea, chlamydia, syphilis, and trichomoniasis were 21%, 19%, 24%, and 51%, respectively. Seventy-four percent were positive for at least 1 STI and 43% had multiple STI infections. High-risk sexual behaviors were found to be common among the women, including low and inconsistent use of condoms, with most of them attributing this to unavailability, dislike by or familiarity with clients, and being drunk and/or high on marijuana.STIs are prevalent among FSWs in Goroka and Kainantu in the EHP and are maintained by widespread high-risk sexual behaviors, including low use of condoms. Implications for their spread through the highway warrants increased efforts in intervention. Apart from a need to promote condom acceptance, distribution, and use, other high-risk sexual behavior and correlates identified in this study provide important considerations for intervention and control in this population.