Objective: Gender-affirming hormonal treatment (HT) in trans people changes physical appearance. Muscle mass and strength are important aspects of physical appearance, but few data exist on the effect of HT on grip strength and musc le mass. This study aimed to investigate the change in grip strength in trans peopl e during the first year of HT and to study the possible determinants of this change and th e associations between changes in grip strength, lean body mass and bone mineral density (BMD). Design and methods: A multicenter, prospective study was performed, including 249 transwomen and 278 transmen. Grip strength, lean body mass and BMD were measured at baseline and after 1 year. Results: After 1 year of HT, grip strength decreased with −1.8 kg (95% CI −2.6; −1.0) in transwomen and increased with +6.1 kg (95% CI +5.5; +6.7) in tr ansmen. No differences in grip strength change was found between age groups, BMI group s, hormonal administration routes or hormone concentrations. In transmen, i ncrease in grip strength was associated with increase in lean body mass (per kg increase in grip strength: +0.010 kg, 95% CI +0.003; +0.017), while this was not found in transwomen (per kg increase in grip strength: +0.004 kg, 95% CI −0.000; +0.009). Change in grip strength was not associated with change in BMD in transwomen and transmen. Conclusions: After 1 year of HT, grip strength decreased in transwomen, and increased in transmen. In transmen only, change in grip strength was associa ted with change in lean body mass.