Abstract Context 46,XX patients with classic congenital adrenal hyperplasia (CAH) are exposed to elevated androgens in utero causing varying levels of virilization. The majority undergo feminizing genitoplasty early in life, with potential impact on sexual function and health-related quality of life (HRQoL). Objective We aimed to determine how sexual and lower urinary tract function, body image, and global HRQoL differs between patients with classic CAH and controls and to characterize how gynecologic anatomy contributes to outcomes. Methods 36 patients with classic CAH and 27 control women who were matched for age, race, and marital status underwent standardized gynecological examination and validated questionnaires. The responses were analyzed in relation to gynecological measurements, genotype, and disease status. Results Compared with controls, patients with CAH were more likely to have sexual dysfunction (P = 0.009), dyspareunia (P = 0.007), and other pelvic pain (P = 0.007); were less likely to be heterosexual (P = 0.013) or ever have been sexually active (P = 0.003); had poorer body image independent of body mass index (P < 0.001); and had worse HRQoL in the areas of general health (P = 0.03) and pain (P = 0.009). The patients with CAH had smaller vaginal calibers and perineal body lengths and larger clitoral indexes when compared with controls (P < 0.001). A larger vaginal caliber in CAH patients was associated with better overall sexual function (P = 0.024), increased sexual satisfaction (P = 0.017), less pain (P < 0.001), and greater number of sexual partners (P = 0.02). Conclusions 46,XX patients with CAH have increased rates of sexual dysfunction, poor body image, and poor HRQoL, which is mitigated by having a larger vaginal caliber. Management aimed at optimizing vaginal caliber might improve sexual function.