OBJECTIVES: To identify cost consequences and cost effectiveness of R-MCP (rituximab, mitoxantrone, chlorambucil, prednisolone) vs. MCP from the perspective of a third party payer in Germany (statutory sickness fund).METHODS: Resource utilization data on 329 patients were collected in parallel to a RCT and analyzed for the treatment phase (8 months). In addition, an interim analysis of the subsequent observation period was conducted. Data for initial chemotherapy, chemotherapy administration, treatment of adverse events, treatment of complications/progressive disease, subsequent chemotherapies and treatment for other reasons were collected. Several sensitivity analyses were performed to address different cost environments and discounting scenarios. RESULTS: Mean cost of the treatment phase in the base case analysis was €35,600 for R-MCP and €21,500 MCP per patient (p <0.0001). More treatment cycles were administered in the R-MCP arm (1,026 MCP, 1,237 R-MCP). Mean cost per patient and active treatment cycle was €4,900 for R-MCP and €3,300 for MCP (p <0.0002). Mean observation period after end of initial treatment were 26.9 months for R-MCP and 25.8 months for MCP. Costs for treatment of adverse events, new chemotherapies, treatment of progressive disease and other reasons was substantially reduced in the R-MCP arm. This resulted in mean (undiscounted) cost per patient in the observation period of €17,900 for R-MCP and €30,700 for MCP (p <0.01). Overall costs were €51,100 for R-MCP and €53,900 for MCP (p = 0.6). Clinically, R-MCP resulted in statistically significant superior response rate, event free survival and overall survival. CONCLUSION: Initially higher treatment costs of R-MCP were compensated by savings due to reduced toxicity and better efficacy after slightly more than two years. Combined with the clinical superiority of R-MCP, this regime is likely to prevail as the dominant treatment strategy compared to MCP alone at the final analysis (at four years observation).