OBJECTIVES: New designs of female condoms have been developed to lower cost and/or improve acceptability. To secure regulatory approvals, clinical studies are required to verify performance. We aimed to assess the functional performance and safety of two new female condom types - Velvet and Cupid2 female condom - against the existing FC2 female condom. STUDY DESIGN: This was a three-period crossover, randomized noninferiority clinical trial with 300 women randomized to condom-type order in one South African site. Primary end points were total clinical failure and total female condom failure. Noninferiority of component modes, clinical breakage, nonclinical breakage, slippage, misdirection and invagination were also determined. Safety data were also assessed for each female condom. Participants were asked to use five of each female condom type and to collect information on use in a condom diary at home and were interviewed after use of each type. Frequencies and percentages were calculated by condom type for each failure mode, and differences in performance of the three female condoms using FC2 as reference, with 95% confidence intervals, were estimated using generalized estimating equation models. RESULTS: A total of 282 (94%) participants completed follow-up, using at least one condom of each type. Total clinical failure (clinical breakage, invagination, misdirection, slippage) was <5% for all female condoms: FC2 (4.50%), Cupid2 (4.79%) and Velvet (3.93%). Noninferiority was demonstrated for all condom failure modes for the two new female condoms with respect to FC2, within the margin of 3% difference in mean failure, at the 5% significance level. CONCLUSION: Noninferiority for the two new female condoms was demonstrated with respect to the marketed FC2. These data are used to support manufacturer dossiers for World Health Organization (WHO)/United Nations Population Fund (UNFPA) prequalification. IMPLICATIONS: Data from this study have been submitted to WHO/UNFPA and will contribute to the prequalification submission requirements for the Cupid2 and Velvet female condoms.