Hematopoietic stem cell transplantation (HSCT) is an established treatment for a variety of malignant diseases, as well as a small proportion of non-malignant disorders. The treatment before the HSCT (called conditioning) can be either myeloablative (MAC) or given with reduced intensity (RIC). MAC is associated with high toxicity due to high doses of chemotherapy with or without total body irradiation (TBI), and is used in both autologous and allogeneic HSCT. In autologous HSCT the patient is the donor, and in allogeneic HSCT the donor is a sibling or an unrelated donor. RIC regimens are associated with reduced toxicity and are only for patients undergoing allogeneic HSCT. Both autologous and allogeneic HSCT have a strong effect on the patients’ health-related quality of life (HRQL). The two studies in this thesis were initiated when RIC was introduced at a hematological department in south-east Sweden in 2001. The overall purpose was to evaluate HRQL in patients undergoing HSCT. The studies covered the whole inpatient period and the following three years in order to have a comprehensive assessment of the patients’ HRQL over time. HRQL was assessed 13 times from baseline up to three years after HSCT with the instrument EORTC QLQ-C-30. The instrument consists of 30 items divided into three major domains: functional status, symptom status, and global health/QoL. Almost all functional scales, global health status/QoL, symptom scales and single items were significantly affected in the two studies during the first two to three weeks from baseline. The symptoms that patients estimated to be the most severe in the studies were nausea and vomiting, loss of appetite, fatigue, and diarrhea. Two months after HSCT nearly all functional scales, global health status/QoL, symptom scales and single items in Study I had returned to the same value as at baseline in patients undergoing autologous HSCT. It took up to two years for patients undergoing allogeneic HSCT in Study II to return to the same value as at baseline. For patients in Study I, role-, emotional-, and social function, fatigue and dyspnea had significantly improved at the 3-year follow-up compared to baseline, whereas role function was the only function that had improved in Study II. Patients with lymphoma in Study I experienced significantly worse HRQL in week 2 and appetite loss at month 2 than patients with multiple myeloma (MM). Patients treated with MAC in Study II had significantly worse fatigue and nausea and vomiting at baseline and pain, sleep disturbance, appetite loss and diarrhea at weeks 3 and 4 than patients treated with RIC. Patients with extensive chronic Graft versus Host Disease (GvHD) in Study II reported significantly impaired physical function, role function, and global health status/QoL than patients with limited or no chronic GvHD. These results provide a good overview of patients’ symptoms and HRQL during and after HSCT and indicate when they require increased support from healthcare professionals. The results also demonstrate the importance of close follow-ups during the first year after HSCT in order to improve preventive interventions. The quick recovery of patients in Study I suggests that the extensive treatment is well tolerated.