OBJECTIVES: Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma, typically treated with a rituximab-containing immunochemotherapy regimen. The randomized, phase 3 GALLIUM trial showed an increase in progression-free survival (PFS) for patients with previously untreated FL when receiving obinutuzumab plus chemotherapy (G-chemo) compared to rituximab plus chemotherapy (R-chemo). The objective of this study is to assess the cost-effectiveness of G-chemo versus R-chemo for previously untreated FL from a US payer perspective. METHODS: A three-state partition survival model was developed using GALLIUM PFS and overall survival (OS) data to model long-term outcomes over a 30-year time frame. CDC life tables were used to inform background mortality rates for patients with FL. Adverse event frequencies were obtained from trial data, and costs were calculated using Average Sales Price (ASP) and Medicare reimbursement rates. Utility estimates for pre-progressive and post-progressive states were obtained from literature. RESULTS: Treatment with G-chemo resulted in an incremental gain of 0.84 life-years, or 0.68 quality-adjusted life years (QALYs) compared to R-chemo. The total costs over a 30-year horizon were $308,527 for G-chemo and $293,356 for R-chemo, resulting in an incremental cost of $15,171. Treatment with G-chemo was associated with higher treatment costs, which were offset somewhat by lower post-progression costs. Adverse event frequencies and costs were also higher for G-chemo. The incremental cost-effectiveness ratio (ICER) for G-chemo versus R-chemo was $22,161 per QALY gained, which is cost-effective at a $50,000 per QALY threshold. The one-way sensitivity analysis showed that model results were most sensitive to PFS parameters for G-chemo and R-chemo, followed by drug costs and patient utilities. CONCLUSIONS: Treatment with G-chemo is likely cost-effective compared to R-chemo from a US payer perspective in the setting of previously untreated FL. The higher treatment costs of G-chemo are offset by gains in QALYs and delayed progression of disease.