OBJECTIVES:  The objective of this study was to estimate the cost-effectiveness of obinutuzumab in combination with chlorambucil in first line treatment of chronic lymphocytic leukemia (CLL) in Greece, in patients unsuitable for full-dose fludarabine therapy. METHODS:  A three-state Markov model was locally adapted to reflect the treatment pathway and resource use within the Greek health care setting. The model compared obinutuzumab + chlorambucil (GClb) versus rituximab + chlorambucil (RClb), chlorambucil monotherapy (Clb), ofatumumab + chlorambucil (OClb) and rituximab + bendamustine (RBenda). Patient demographics and clinical data were taken from the CLL11 clinical trial and indirect analysis. Data on resource use were elicited from an expert panel of 6 hematologists with the Delphi technique. Unit costs were taken from officially published Greek sources (Ministry of Health, Social Insurance Funds). Utility data were taken from a published UK study. Only direct costs were considered in the analysis and the cost base year was 2016. The time horizon was lifetime and the perspective adopted was the societal. Future costs and outcomes were discounted at 3.5%. Probabilistic sensitivity analysis (PSA) was performed to test robustness of model results. RESULTS:  GClb was associated with higher mean costs (€24,874) but also with higher life years gained (LYs -5.70) and quality adjusted life years (QALYs) 3.95 versus all comparators. The incremental cost effectiveness ratio (ICER) of GClb versus RClb was estimated at €15,679 per LY and €16,614 per QALY gained. The respective ICERs versus Clb, OClb and RBenda were estimated at €17,258, €9,587 and €9,445 per LY and €19,269, €9,967 and €10,026 per QALY gained. PSA showed that the probability of GClb being cost effective at a threshold of €50,000 per QALY was 98.9%. CONCLUSIONS:  GClb appears to be a cost effective treatment option versus all comparators in first line treatment of CLL in the Greek health care setting.