To assess the potential for decreased condom use as pre-exposure prophylaxis (PrEP) is scaled-up in Latin America, we examined HIV prevention method preferences (neither PrEP nor condoms, condoms only, PrEP only, or PrEP with condoms) within 1302 sexual partnerships reported by 397 HIV-negative men who have sex with men (MSM) and transgender women (TW) in Tijuana, Mexico. Using PrEP with condoms (56%) was preferred to using condoms only (24%), using PrEP only (17%), and using neither PrEP nor condoms (3%). Compared to using condoms only, using PrEP only was preferred within primary (adjusted odds ratio [AOR] = 4.13, 95% confidence interval [CI] 1.92, 8.90) and condomless sex practicing (AOR = 6.97, 95% CI 3.92, 12.40) partnerships, suggesting PrEP use may not displace condom use among MSM and TW in Tijuana and other similar settings.