OBJECTIVES: Recurrent disease represents a clinical challenge in the treatment of indolent non-Hodgkin’s lymphoma (iNHL) and mantle cell lymphomas (MCL). The combination of fludarabine+rituximab (FR) is among the current treatments for relapsed iNHL and MCL. The objective of this study was to assess the economic impact of bendamustine-rituximab (BR) compared to FR in the treatment of relapsed iNHL and MCL in Canada. METHODS: The cost-effectiveness of BR compared to FR in the treatment of relapsed iNHL/MCL was assessed over a lifetime horizon using a time-dependent Markov model. The Markov model comprises three health states: progression-free (PF), progressive disease (PD) and death. The length of each Markov cycle is one month. All patients start in the PF state and could move to other health states thereafter, according to the respective efficacy of each treatment. The model also takes into account the incidence of treatment-induced adverse events including grade 4 haematological events and all grades nausea. Utility values associated with each health state and adverse events were used to estimate the number of QALYs associated with each treatment. Analyses were conducted from both a Canadian Ministry of Health (MoH) and a societal perspective. RESULTS: Compared with FR, BR is associated with ICERs of $38,821 per QALY and $45,809 per QALY, from a MoH and societal perspective respectively. Exhaustive sensitivity analyses confirm the robustness of the base-case scenario. Specifically, results of the probabilistic sensitivity analysis indicated that, according to a willingness to pay of $50,000, BR remains a cost-effective strategy in 100% and 90.2% of the simulations. CONCLUSIONS: This economic evaluation demonstrates that bendamustine in combination with rituximab is a cost-effective strategy in the treatment of relapsed iNHL/MCL when compared with fludarabine in combination with rituximab.