In formulating the second national strategic plan for prevention of HIV/AIDS in the Islamic Republic of Iran a more evidence-based approach was needed. This paper reports on a systematic review of the local evidence about the determinants of HIV/AIDS transmission in 3 categories poor knowledge and negative attitudes about HIV transmission; injection drug use; and sexual promiscuity. Of 93 reports reviewed, 53 met the inclusion criteria. Information about the prevalence and magnitude of effect for the 3 risk determinants at the national and regional level was scarce. Heterogeneity between studies, even in the same sub-population, was significant. An improved research base and better sharing of information are needed within countries of the Eastern Mediterranean Region.