In the randomized phase 3 GALLIUM trial, first-line treatment with obinutuzumab (GA101; G) plus chemotherapy (G + chemo) resulted in superior progression-free survival (PFS) compared with rituximab plus chemotherapy (R + chemo) for patients with follicular lymphoma (FL). G + chemo was found to be cost-effective when compared with R + chemo (incremental cost-effectiveness ratio [ICER] of approximately $2,300 per quality-adjusted life-year [QALY] gained). Two rituximab biosimilars, rituximab-abbs (Ra) and rituximab-pvvr (Rp), have been approved by the FDA for use in this setting. However, the cost-effectiveness of G + chemo versus Ra + chemo and Rp + chemo has not yet been estimated. To evaluate the cost-effectiveness of G + chemo versus Ra + chemo and Rp + chemo in the first-line treatment of FL. We adapted an existing Markov model that compared G + chemo with R + chemo, using investigator-assessed PFS and postprogression survival data from the GALLIUM trial to model overall survival. All patients in the study received induction chemoimmunotherapy with either G + chemo or R + chemo, with responders then receiving obinutuzumab or rituximab maintenance therapy for 2 years or until disease progression. We assumed that the efficacy and safety of the rituximab biosimilars plus chemotherapy were the same as the R + chemo arm of the GALLIUM study. Drug utilization and treatment duration were also derived from GALLIUM. Health care costs were based on Medicare reimbursements, and drug costs were average sale prices for intravenous therapies or wholesale acquisition costs for oral therapies used after progression. Utility estimates were based on the GALLIUM trial data and published literature. Sensitivity analyses were conducted to assess the key drivers of the model and uncertainty in the results. Treatment with G + chemo led to an increase of 0.93 QALYs relative to rituximab biosimilars plus chemotherapy (95% credible range [CR] = 0.36-1.46). The total cost of G + chemo was $191,317, whereas the total costs of Ra + chemo and Rp + chemo were $164,340 (Δ14.1%) and $169,755 (Δ11.3%), respectively, with G + chemo resulting in incremental costs of $26,978 (95% CR = $19,781-$33,119) and $21,562 (95% CR = $14,473-$28,389), respectively. The incremental total drug and administration costs were $32,678 (Δ25.4%) and $27,263 (Δ21.2%) for G + chemo versus Ra + chemo and G + chemo versus Rp + chemo, respectively. There were cost savings of $7,050 (Δ-12.4%) related to disease progression for G + chemo ($56,727) compared with Ra + chemo and Rp + chemo ($63,777). ICERs were $28,879 and $23,082 per QALY gained for G + chemo versus Ra + chemo and Rp + chemo, respectively. In probabilistic sensitivity analyses, G + chemo was cost-effective at the $50,000 and $100,000 per QALY thresholds versus both Ra + chemo (88% and 98% probabilities of cost-effectiveness, respectively) and Rp + chemo (93% and 98%, respectively). G + chemo is projected to be cost-effective versus rituximab biosimilars plus chemotherapy in the United States as first-line treatment for FL, driven by increased QALYs for G + chemo and cost savings from delayed disease progression. This study was funded by Genentech, a member of the Roche Group. The study sponsor was involved in study design, data interpretation, and writing of the report. All authors approved the decision to submit the report for publication. Spencer and Guzauskas report fees from Genentech during the conduct of the study. Felizzi was employed by F. Hoffmann-La Roche at the time this study was conducted; Launonen is an employees of F. Hoffmann-La Roche. Felizzi and Launonen previously had share ownership in Novartis. Dawson and Masaquel are employees of Genentech, and they have stock options in F. Hoffmann-La Roche. Veenstra reports fees from Genentech, during the conduct of this study and outside of the submitted work. This work was presented, in part, at the AACR Virtual Meeting Advances in Malignant Lymphoma meeting (virtual; August 17-19, 2020) and the SOHO annual meeting (virtual; September 9-12, 2020).