BACKGROUND: Bone loss is a frequent complication after liver transplantation. OBJECTIVE: To investigate whether vitamin D receptor gene polymorphism influences bone loss in men after liver transplantation. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENTS: 55 male candidates for liver transplantation. MEASUREMENTS: Lumbar spine bone mineral density was measured before and 3, 6, 12, and 24 months after liver transplantation. Vitamin D receptor genotype was determined by restriction endonuclease Bsml. RESULTS: Vitamin D receptor genotypes were significantly associated with post-transplantation changes in bone mineral density (P = 0.028). Within 3 months after transplantation, patients with the genotypes Bb or BB showed a vertebral bone loss substantially greater than that in patients with the bb genotype (between-group difference in the percentage change with respect to baseline bone mineral density, 3.7% [95% CI, 0.6% to 6.9%1). In 3 to 24 months after transplantation, bone mineral density increased steadily in the three allelic groups. CONCLUSIONS: Vitamin D receptor gene polymorphism influences bone loss after liver transplantation. Patients with the bb genotype are, to some extent, protected against post-transplantation bone loss.