Previous research demonstrated that physical health-related quality of life (HRQOL) improves after liver transplantation, but improvements in mental HRQOL are less dramatic. The aim of this study was to test the effects of physical HRQOL, time post-transplant, and gender on pre- to post-transplant change in anxiety and depression. Longitudinal HRQOL data were prospectively collected at specific times before and after liver transplantation using the SF-36® Health Survey (SF-36), Center for Epidemiologic Studies Depression Scale (CES-D), and Beck Anxiety Inventory (BAI). Within-subject change scores were computed to represent the longest follow-up interval for each patient. Multiple regression was used to test the effects of baseline score, time post-transplant, gender, and SF-36 physical component summary scores (PCS) on change in BAI and CES-D scores. About 107 patients (74% male, age∈= ∈54∈±∈8 years) were included in the analysis. Time post-transplant ranged 1 to 39 months (mean∈=∈9∈±∈8). Improvement in symptoms of anxiety and depression was greatest in those patients with the most severe pre-transplant symptoms. Significant improvement in symptoms of depression occurred after liver transplant, but the magnitude of improvement was smaller with time suggesting possible relapse of symptoms. Better post-transplant physical HRQOL was associated with a greater reduction in symptoms of anxiety and depression after liver transplantation. This demonstrates clear improvements in post-transplant mental HRQOL and the significant relationships between physical and mental HRQOL. © 2007 The Society for Surgery of the Alimentary Tract.