The overall costs of pediatric stem cell transplantation (SCT), including donor search and costs during the first year post-SCT, were calculated in a cohort of 141 consecutive children undergoing SCT in a single institution. Costs were correlated with patient and transplantation characteristics and with a risk score for transplantation-related mortality. Cost-effectiveness was calculated based on the overall cost per surviving patient. Life-years gained were extrapolated from overall survival, and the costs per expected life-year gained were calculated. The overall median cost was €136,382 (175,815$), with a wide range, of €26,897 (34,679$) to €601,348 (775,343$). Increased costs were significantly associated with age, use of donors other than matched siblings, and advanced disease. There was a strong correlation of costs with a simple transplantation-related mortality risk score; median total costs were €89,550 (115,463$) for a score of 0, €127,349 (164,179$) for a score of 1, €156,578 (201,861$) for a score of 2, and €274,915 (354,499$) for a score of 3 (P < .001). Cost-effectiveness decreased with increasing transplantation-related mortality risk score; costs per survivor increased from €93,209 (120,200$) for a score of 0 to a maximum of €1,216,348 (1,568,579$) for a score of 3. Costs associated with pediatric SCT vary substantially; however, the combination of variables such as age, disease, and donor type is predictive of costs and cost-effectiveness. Costs per life-year gained are within the broadly accepted range in life-threatening hemato-oncologic diseases, even in the most cost-intensive patient cohort.