Graft survival and function early after hand transplantation is good. It remains unknown, however, whether long-term survival is limited by chronic rejection. We here describe the clinical course and the status 5 years after bilateral hand transplantation with emphasis on immunosuppression (IS), function, morphology and graft vascular changes. Clinical observation, evaluation of hand function, skin biopsies, X-ray, ultrasound, angiography, CT angiography, electrophysiologic studies including compound motor and sensory action potentials (CMAP, CSAP) and somatosensory evoked potentials were performed and results recorded at regular intervals. Following reduction of IS one mild (grade II) rejection episode occurred at 4 years. Subsequently, skin histology remained normal and without signs of chronic rejection. Hand function continuously improved during the first 3 years and remained stable with minor improvement thereafter. CMAP and CSAP progressively increased during the observation period. Latencies of the cortical responses were prolonged but amplitudes were within normal range. Investigation of hand vessels revealed no signs of occlusion but showed revascularization of a primarily occluded right radialis artery. Motor and sensory function improved profoundly between years 1 and 5 after hand transplantation. No signs whatsoever of chronic rejection have been observed.