We aim to describe the relationship between sexual orientation identity and medical morbidities in a large sample of male-to-female (MTF) transgender patients. We reviewed medical records of patients presenting for MTF sex reassignment surgery (SRS) by a single, high-volume surgeon from 2011 to 2015. Sexual attraction to men (heterosexual), women (lesbian), or both (bisexual) was asked of each patient. We examined 16 medical morbidities for this analysis. During the study period, 330 MTF transgender patients presented for SRS. The average age at the time of surgery was 38.9 (range 18-76). One hundred and one patients (32%) reported being heterosexual, 110 patients (34%) reported being lesbian, and 108 patients (34%) reported being bisexual. Lesbian patients presented for SRS at older ages (mean = 43 years old) compared with heterosexual patients (mean = 36 years old) and bisexual patients (mean = 37), P < 0.01. No differences were found in the majority of coexisting medical morbidities by sexual orientation identity. Lesbian patients had greater odds of having a history of depression, age-adjusted odds ratio (aOR) = 2.36, 95% confidence interval (CI) 1.26-4.40, compared with heterosexual patients. Lesbian patients had higher odds of being married or partnered, aOR = 2.31, 95% CI (1.27-4.19), compared with heterosexual patients. Heterosexual patients had higher odds of having human immunodeficiency virus (HIV), aOR = 9.07, 95% CI (1.08-76.5) compared with lesbian patients. Sexual orientation identity in MTF transgender patients is variable. The majority of medical morbidities are not associated with sexual orientation identity. Although HIV and depression are common morbidities among MTF patients seeking SRS, the prevalence of these morbidities differs by sexual orientation identity, but these findings need replication. Counseling and future research initiatives in transgender care should incorporate sexual orientation identity and associated risk behavior.