Objective: Autologous stem cell transplantation (ASCT) has improved progression-free survival (PFS) and overall survival in eligible patients with newly diagnosed multiple myeloma (NDMM); however, relapse occurs. Maintenance therapy with lenalidomide (Len-Mt) extends survival and delays relapse and the subsequent initiation of costly second-line regimens. Here, we report the cost-effectiveness of Len-Mt following ASCT from a Dutch healthcare service perspective. Methods: A partitioned survival model was developed to assess the lifetime costs and benefits for patients with NDMM. Efficacy was taken from a pooled meta-analysis of clinical trial data. Costs and subsequent therapy data were taken from sources appropriate for the Dutch market. Results: Lenalidomide produced a quality-adjusted life year gain of 2.46 and a life year gain of 2.79 vs no maintenance treatment. The cost of lenalidomide was partially offset by savings of EUR 77 462 in subsequent treatment costs. The incremental cost-effectiveness ratio of Len-Mt vs no maintenance treatment was EUR 30 143. Key model drivers included subsequent therapies, dosing schedule, and time horizon. Conclusion: Lenalidomide is cost-effective after ASCT vs no maintenance therapy in the Netherlands. By extending PFS, lenalidomide delays the cost burdens associated with relapse and subsequent treatment lines.