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An ongoing study of mother-to-child human transmission in Zambian women (n = 3,160) allowed us to examine the association of medical injections with HIV serostatus while simultaneously accounting for other factors known to be correlated with HIV prevalence. Multi-method data collection included structured interviews, medical record abstraction, clinical examinations, and biological measures. Medically administered intramuscular or intravenous injections in the past five years (but not blood transfusions) were overwhelmmgly correlated with HIV prevalence, exceeding the contribution of sexual behaviors in a multivariable logistic regression. Statistically significant associations with HIV also were found for some demographic variables, sexual behaviors, alcohol use, and sexually transmitted diseases (STD) . The results confirmed that iatrogenic needle exposure, sexual behavior, demographic factors, substance use, and STD history are all implicated in Zambian women’s HIV + status. However, the disproportionate association of medical injection history with HIV highlights the need to investigate further and prospectively the role of health-care injection in sub-Saharan Africa’s HIV epidemic.