OBJECTIVES: To compare hematological toxicity, costs, health-related quality of life (HR-QOL) and outcomes observed in real life in the Belgian Non-Hodgkin Lymphoma (NHL) population receiving 90Y-Zevalin, with model-predicted data at reimbursement on the basis of a clinical trial in heavily pre-treated NHL. METHODS: Twelve of the 13 centers trained for 90Y-Zevalin administration at the time of reimbursement approval participated. All consecutive patients receiving 90Y-Zevalin for Rituximab-relapsed/refractory NHL were included in this 1-year, multi-center, prospective, observational study. QOL-assessments, based on a generic (EQ-5D) and a disease-specific (FACT-LYM) questionnaire, were performed at baseline (date of first administration Rituximab), day 8, month 1, 2 and 3 after baseline. Costing (€, 2008) was based on official tariffs and observed resource use. RESULTS: Over the 2-year recruitment period, thirty patients were included. Only 1 patient received hematopoietic growth factor prophylaxis. Hematological toxicity occurred in 79% of patients, but was generally mild. Grade IV neutropenia was reported in 16% of patients (35% predicted); grade IV thrombocytopenia in 23% (9% predicted) and grade IV anemia was not reported (4% predicted). EQ-5D as well as FACT-LYM assessments suggested no significant changes in HR-Qol over the study period and no impact of hematological toxicity on HR-Qol. The average total cost from the health care payer perspective, covering costs of drugs, drug administration setting and prophylaxis, mounted to €16,886 (Standard error 79 €). Hematological toxicity added €1,191 (Standard error: €528), constituting 7% of total costs (18,076 €). Observed costs were within 2% from predicted costs. Median time to progression (TTP) was 11.7 months (6.8 months predicted). CONCLUSIONS: This observational study confirmed the predicted tolerability profile, costs and outcomes associated with 90Y-zevalin in a real life patient population. Furthermore, the patient numbers treated with 90Y-Zevalin in real life were lower than anticipated (maximum 100 predicted).