MtF total mortality 51% above general population. Deaths mainly from suicide, AIDS, cardiovascular disease, drug abuse, unknown causes. No overall cancer mortality increase but lung and hematological cancers elevated in MtF. Current ethinyl estradiol use triples cardiovascular death risk independently. Past ethinyl estradiol use not linked to higher cardiovascular death. FtM total mortality matches general population. FtM cause-specific mortality matches general population. MtF received high-dose estrogens plus cyproterone acetate 100mg/day. FtM received testosterone esters or gel. Follow-up median 18.5 years in 966 MtF and 365 FtM. Cohort started hormones before 1997 with at least 1-year follow-up. Increased MtF mortality mostly non-hormone-related but ethinyl estradiol raises cardiovascular risk. Post-surgery hormone doses lowered but treatment continued.