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Although systematic reviews of epidemiologic studies have been conducted for condom use and the risk of several sexually transmitted diseases, there have been no such reviews for condom use and syphilis.A systematic literature review of epidemiologic studies published from 1972 to 2008 was conducted to evaluate study methods and measures of association reported for condom use and risk of syphilis.All 12 included studies had significant methodologic limitations. Nine (75%) studies were cross-sectional. Although 11 (92%) studies assessed consistent condom use, no studies assessed correct use or condom use problems, nor did any document exposure to a partner infected with syphilis. Ten studies had insufficient information to distinguish prevalent from incident infections. Two studies that assessed both incident infection and consistent condom use suggested a reduced risk of syphilis with consistent condom use; 1 study was statistically significant.Significant methodologic limitations exist for all reviewed studies of syphilis and condom use. Among the 2 most rigorously designed studies, both suggested a reduced risk of syphilis with consistent condom use. Additional studies incorporating rigorous methods are needed to further assess the effect of condom use on risk of syphilis.