Health-related quality of life (HRQOL), fatigue and psychological distress were prospectively assessed in 248 cancer patients treated with allogeneic (SCT, N=61), or autologous (ASCT, N=69) stem cell transplantation or conventional chemotherapy (CT, N=118) of whom 128 completed the assessments after 3 years. The European Organization for Treatment and Research of Cancer Core Quality of Life Questionnaire and the Hospital Anxiety and Depression Scale were administered nine (SCT/ASCT groups) or seven times (CT group) during the first year. The Fatigue Questionnaire was added at the final assessment. The SCT group displayed greater changes from baseline scores than the ASCT group, with more symptoms in the first months post transplant. A gradual improvement was found in both groups during the following 4-6 months, before stabilizing at baseline levels. Only minor changes were observed after the first year. All groups reported more fatigue than the population values after 3 years (P<0.01). The ASCT group also reported less optimal HRQOL (P<0.01-0.0001). No differences were found in anxiety and depression. Despite a faster recovery during the first months after transplant, the ASCT patients reported poorer functioning and more fatigue compared to the SCT group after 3 years. This suggests a need for a closer follow-up of these patients with special emphasis on functional status and fatigue.