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The aim of the study was to compare reproductive health and high-risk behaviors in female sex workers (FSWs) and single mothers (SMs) in Zambia's two largest cities, Lusaka and Ndola. FSWs were invited from known community hot spots, and sexually active HIV- SMs were referred from infant vaccination services for free and anonymous screening and treatment for HIV and other sexually transmitted infections (STIs) and long acting reversible contraception. A subset completed an interviewer-administered survey. From 2012 to 2016, 1,893 women (1,377 FSWs and 516 HIV- SMs) responded to referrals. HIV prevalence was 50% in Lusaka and 33% in Ndola FSWs. Positive syphilis serology (rapid plasmin reagin) was found in 29%-31% of HIV+ FSWs and 9%-12% of HIV- FSWs and SMs. Trichomonas was more common in Ndola (11%-12%), compared with Lusaka (3%-7%). Antiretroviral therapy (ART) use among HIV+ FSWs was 9%-15%. In all groups, consistent condom use (8%-11%) and modern contraceptive use (35%-65%) were low. Low literacy and reported coercion at first sexual intercourse were common in both FSWs and SMs, as was alcohol use during sex among FSWs. Zambian FSWs and SMs have low condom use and high HIV/STI and unplanned pregnancy risk. Many FSWs and half of SMs are ≥25 years of age, and thus too old for HIV prevention services targeting "adolescent girls and young women" (aged 15-24). Tailored and targeted reproductive health services are needed to reduce HIV, STI, and unplanned pregnancy in these vulnerable women.