Purpose: We assessed the association of receipt of medical gender affirmation services (e.g., hormones, surgery) with HIV and other sexually transmitted disease (STD) prevention and knowledge indicators among transgender youth. Methods: A United States online sample of sexually experienced transgender youth ages 13-24 years (N = 1029) in 2018 completed a cross-sectional survey, including questions about sociodemographics, medical gender affirmation, and HIV and STD prevention outcomes (HIV testing, STD testing, pre-exposure prophylaxis [PrEP] awareness, and nonoccupational postexposure prophylaxis [nPEP] awareness). Logistic regression models were fit to assess the association of medical gender affirmation with HIV and STD prevention outcomes. Interaction terms and stratified models assessed differences in the association between medical gender affirmation and outcomes by gender identity. Results: Participants' mean age was 19.1 (standard deviation = 2.7), 45% were transgender female, 29% transgender male, 26% nonbinary, 53% were youth of color, and 19% accessed medical gender affirmation services. Medical gender affirmation was associated with increased odds of STD testing (adjusted odds ratio [aOR] = 1.90; 95% confidence interval [CI] = 1.33-2.73) with no significant interactions by gender identity. Associations between medical gender affirmation and awareness of PrEP and nPEP varied by gender identity. Among transgender male youth, medical gender affirmation was associated with awareness of PrEP (aOR = 2.65; 95% CI = 1.50-4.71) and nPEP (aOR = 2.03; 95% CI = 1.12-3.71). Among nonbinary youth, medical gender affirmation was associated with awareness of PrEP (aOR = 3.47; 95% CI = 1.26-11.27). Conclusion: Medical gender affirmation was associated with uptake and awareness of sexual health services. Bolstering medical gender affirmation for transgender youth may also bolster preventive health services broadly.