OBJECTIVES: Dutch policy requires evidence from outcomes research for the assessment of appropriate drug use and real-world cost-effectiveness. We investigated whether a population-based patient registry could improve the feasibility of outcomes research in multiple myeloma compared to a retrospective cohort study. METHODS: Two methods were used to investigate the feasibility of outcomes research. First, we conducted outcomes research for bortezomib in multiple myeloma (n=139) by retrospectively collecting detailed data from hospital medical records in 38% of all Dutch hospitals. Second, we conducted outcomes research by using a population-based registry for haematological malignancies (PHAROS) covering 40% of the Netherlands. Up till now, the registry contains 3093 patients, including 802 patients with multiple myeloma. RESULTS: In the retrospective bortezomib study, it was possible to gather data on drug and resource use in everyday practice. However, due to great patient heterogeneity, extensive treatment variation (>10 drugs in >20 combinations) and missing prognostic information (e.g. 71% missing serum β2-microglobulin levels), it was impossible to estimate incremental cost-effectiveness of bortezomib. The PHAROS population-based registry also provided data on drug and resource use in everyday practice. Like the retrospective study, the registry revealed extensive treatment variation. This, in combination with great patient heterogeneity, challenged the feasibility to identify appropriate groups of comparable patients to calculate cost-effectiveness. CONCLUSIONS: Compared to a clinical trial, outcomes research in multiple myeloma is complicated by extensive treatment variation and wide patient heterogeneity. The PHAROS registry provides better generalisable outcomes research results, but many challenges remain in data analysis. Nevertheless, the greater number of real-world patients might provide the opportunity to obtain a sufficiently valid cost-effectiveness estimate by using comprehensive modeling techniques and different data sources.