AbstractDesvenlafaxine exposure in Korean and US populations was compared using population pharmacokinetic (PK) analysis. Data from a single‐ and multiple‐dose study of desvenlafaxine (50, 100, and 200 mg) in 30 healthy Korean subjects were added to a population PK model previously developed using sparse PK samples from patients with major depressive disorder, including 140 Korean patients, combined with rich PK data from healthy volunteers. The structural PK model was an open 1‐compartment linear disposition model with parallel first‐order and 0‐order inputs. The effects of Korean status on apparent oral clearance (CL/F) and apparent volume of distribution (V/F) were tested against the base model separately. External validation results indicated good agreement between the model predictions and observed desvenlafaxine concentrations for Korean subjects. The geometric mean CL/F and V/F of Korean subjects were 9.1% and 16.7% lower, respectively, than those of US subjects, who had a 20% higher mean body weight. Results for patients with major depressive disorder were similar. There were no meaningful differences for weight‐normalized CL/F and V/F values between Korean and US subjects or patients. The minor differences in CL/F and V/F observed between Korean and US populations appear to be solely due to lower body weights in the Korean population.