The male condom, which consists of a thin sheath placed over the glans and shaft of the penis, is designed to prevent pregnancy by providing a physical barrier against the deposition of semen into the vagina during intercourse. Beginning in the 1990s, nonlatex male condoms made of polyurethane film or synthetic elastomers were developed as alternative male barrier methods for individuals with allergies, sensitivities or preferences that prevented the consistent use of condoms made of latex. The review sought to evaluate nonlatex male condoms in comparison with latex condoms in terms of contraceptive efficacy, breakage, slippage, safety and user preferences. We searched the the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE using PubMed, EMBASE, Popline, and LILACS for randomized controlled trials of nonlatex condoms. The references of eligible publications were assessed for inclusion. We also wrote to the manufacturers of nonlatex condoms and known investigators in an attempt to locate any other published or unpublished trials not identified in our search. The review included all randomized controlled trials identified in the literature search that evaluated a male nonlatex condom made of polyurethane film or synthetic elastomers in comparison with a latex condom. We evaluated all titles and abstracts located in the literature searches for inclusion in the review. Two reviewers independently extracted data from the identified studies. We entered and analyzed data with RevMan 4.1. Peto odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for the outcomes contraceptive efficacy, condom breakage and slippage, discontinuation of use, safety and user preference. The number of condoms, men, or women was used as the denominator for the ORs. Contraceptive efficacy, early discontinuation, and safety outcomes were also measured with survival analysis techniques and entered into "Additional tables." While the eZ.on condom did not protect against pregnancy as well as its latex comparison condom, no differences were found in the typical-use efficacy in the comparisons between the Avanti and the Standard Tactylon and their latex counterparts. The nonlatex condoms were associated with higher rates of clinical breakage than their latex comparison condoms. The statistically significant odds ratios for clinical breakage for the nonlatex condoms versus their latex comparisons ranged from 2.6 (95% CI: 1.6 to 4.3) to 5.0 (95% CI: 3.6 to 6.8). Few adverse events were reported. In almost all of the comparisons, substantial proportions of participants preferred the nonlatex condom or reported that they would recommend its use to others. Although the nonlatex condoms were associated with higher rates of clinical breakage than their latex comparison condoms, the new condoms still provide an acceptable alternative for those with allergies, sensitivities or preferences that might prevent the consistent use of latex condoms. The contraceptive efficacy of the nonlatex condoms requires more research.