Osteoporosis is prevalent in end-stage liver disease, but data on long-term changes in bone mineral density (BMD) and related fracture incidence are scarce after orthotopic liver transplantation (OLT). We evaluated BMD changes up to 5 years in consecutive recipients of a successful OLT at the Leiden University Medical Centre between 2000 and 2011, in whom sequential BMD data were available. Spinal radiographs were available at time of screening and at six and twelve months post-OLT and were assessed for vertebral fractures by two independent observers using Genant's semi-quantitative method. Patients were excluded from the study when started on bisphosphonates. 201 patients (71% men), median age 53 years (range 18–70 years) were included in the study. Most common liver pathology was viral (27%) or alcoholic liver disease (25%). All patients received prednisone for at least 6 months after transplantation and the majority either tacrolimus or cyclosporine for immunosuppression. At time of screening for OLT, osteoporosis and osteopenia were found in respectively 18 and 36% of patients at the lumbar spine (LS) and in respectively 9 and 42% at the femoral neck (FN). T-scores declined significantly at both sites 6 months after OLT, but increased thereafter at the LS, reaching pre-transplant values at 2 years, and remaining stable thereafter. FN T-scores remained consistently lower than pre-transplant values. The prevalence of vertebral fractures increased from 56% at screening to 71% at one year after OLT, with a fracture incidence of 34%. BMD changes did not predict fracture risk. Osteoporosis, osteopenia and vertebral fractures are prevalent in patients with end-stage liver disease. An overall decline in BMD is observed within the first 6 months after OLT, with subsequent recovery to pre-transplant values at the LS, but not at the FN. Vertebral fracture risk is high after OLT regardless of changes in BMD. © 2014 American Society for Bone and Mineral Research