OBJECTIVES:  Maintenance treatment with Rituximab (MabThera) has been shown a cost-effective and / or cost-saving treatment option, when compared with alternative treatment strategies for treating patients with Non-Hodgkins Lymphoma (NHL) in several countries. The objective of this study is to identify whether maintenance with Rituximab in first line NHL patients represents a cost-effective treatment option for the Greek Healthcare system. METHODS: A cost-effectiveness Markov model that compared maintenance with Rituximab versus observation was applied after adapting for local cost data from published sources. Clinical data were derived from PRIMA and EORTC 20981.  RESULTS:  Patients treated with Rituximab remained in Progression Free state for an additional 1.91 years and displayed an additional  1.61 QALYs versus observation. Mean Total Cost per patient in the Rituximab maintenance arm was calculated at €79,721 versus €67,928 in the observation arm. Mean total cost of PFS including the cost of Adverse Events was €71.95 for the Rituximab group and €57.44 for the observation group. Mean Supportive Care costs for the Progression-Free state were € 18,193 for patients on Rituximab and €20,168 for patients on observation. Mean supportive care cost of progression was € 7,766 for the Rituximab group and €10,483 for the observation group.  ICERs for Rituximab maintenance were €8,679 per QALY gained and €7,866 per LYG gained, which are both below the common cost-effectiveness thresholds used by Health Technology Assessment (HTA) agencies worldwide. CONCLUSIONS:  Maintenance treatment with Rituximab is clinically more effective and economically more cost-effective than existing treatments for patients with NHL in the Greek healthcare setting. Full reimbursement of Rituximab maintenance treatment for patients with NHL by Social Security Funds would constitute an effective use of their – scarce – resources.