OBJECTIVES: The Dutch reimbursement policy for expensive inpatient medicines requires outcomes research after four years of temporary reimbursement. Based on a retrospective study, we explored the cost-effectiveness of bortezomib for relapsed/refractory multiple myeloma in Dutch daily practice. METHODS: Detailed clinical data from a real-world cohort of 72 patients treated with bortezomib and 67 patients never treated with bortezomib were collected from medical records. Validity of the incremental cost-effectiveness was assessed by comparing baseline prognosis between bortezomib and non-bortezomib patients. Clinical effectiveness was evaluated by comparing Kaplan-Meier survival estimates. Costs of resource use from a hospital perspective were based on patient-level data. RESULTS: Prognostic factors for bortezomib patients were significantly different compared to non-bortezomib patients. Incremental analyses for bortezomib versus non-bortezomib patients were therefore not performed. Total mean costs and median survival from start of relapsed/refractory treatment for bortezomib patients were €84,042 and 33.2 months. Bortezomib accounted for 21% of total costs among these patients. For non-bortezomib patients, total mean costs and median survival from start of relapsed/refractory treatment were €54,435 and 21.6 months.  The proportion of patients still in follow-up at the end of data collection was slightly higher in bortezomib versus non-bortezomib patients (51% vs 46%). Total mean costs for bortezomib patients did not differ significantly when excluding patients still in follow-up. For non-bortezomib patients, total mean costs differed significantly when excluding patients still in follow-up, mainly due to high costs of lenalidomide treatment, stem cell transplants and inpatient hospital stays. CONCLUSIONS: Our real-world data challenged the assessment of the incremental cost-effectiveness of bortezomib versus other treatments in the indication of relapsed/refractory multiple myeloma. It was possible to estimate the cost and effects for bortezomib patients in daily practice to determine the real-world value. Data synthesis incorporating effectiveness for the relevant comparator might facilitate estimation of a valid ICER.