Context: Individuals with gender dysphoria can receive gender-affirming h ormone therapy. Different guidelines mention a severe risk of liver injury within the first months af ter the start of treatment with anabolic androgenic steroids, anti-androgens, and oral contraceptives, which is pot entially fatal. Objective: The incidence of liver injury in a transgender population usin g gender-affirming hormone therapy. Design: Multicentre prospective study with 1933 transgender individual s, who started with hormone therapy between 2010 and 2020. Methods: The following parameters were analysed before hormone therapy, after 3 months, and after 12 months of hormone therapy: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT). Both male and female reference values were considered. Liver injury was defined as either an elevation of 2× upper limit of normal (ULN) of ALP, 3× ULN of ALT, or 3× ULN of AST. Results: 889 transgender women and 1044 transgender men were included i n the analysis. The incidence of liver injury within 12 months after the start of hormone therapy, wit hout attribution to alcohol abuse, medical history, or comedication was 0.1 and 0.0%. in transgender women according t o female and male reference intervals respectively, and 0.6 and 0.4% in transgender men (female and male reference intervals). Conclusion: The incidence of liver injury is found to be very low. We, the refore, conclude that liver enzyme monitoring within the frame of the risk of liver injury due to hormone the rapy is not necessary for a transgender population.