Background: Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard of care for diffuse large b-cell lymphoma (DLBCL). However, adding rituximab has increased treatment costs. Thus, development of biosimilars help provide more affordable care. Though rituximab-abbs was studied primarily in the follicular lymphoma population, in 2018 the FDA approved this drug as the first biosimilar for all indications of the reference product based on extrapolation. However, there are no clinical trials studying the effectiveness and safety of rituximab-abbs in DLBCL in the U.S. Methods: This is a data-only, non-inferiority study to compare two-year overall survival (OS) and the incidence of serious adverse events (AEs) between rituximab-abbs and its reference product (RP) as R-CHOP among adult patients with newly diagnosed DLBCL, with an index date from December 1, 2018-December 31, 2020. Non-inferiority will have a margin set to the upper limit of 5% for serious AEs, and a lower limit of 5% for OS. To assess for safety, we are following up on AEs until end of patient’s Kaiser Permanente (KP) membership, death, six months after last rituximab dose, or December 2022 for all AEs except infusion reactions. For infusion reactions only, the follow up is 1 day. To assess for efficacy, we are following up on OS until end of patient’s KP membership, death, December 2022, or two years. Results: 535 patients were enrolled; 240 patients received RP rituximab and 295 patients received rituximab-abbs. The median time of follow up was 730 days, or 2 years (range in days, 2.0-730). Complete response was similar in the RP rituximab group and the rituximab-abbs group (70.4% vs. 77.3% respectively, p = 0.07). Additionally, partial response was also similar among the two products (19.2% vs. 16.9%, p = 0.51). The Kaplan-Meier two-year survival curve was also similar between the two products (p = 0.52), demonstrating no difference. Further statistical analysis confirmed the non-inferiority of the biosimilar products for survival. Infusion reaction adverse events (13.8% vs. 11.2%, p = 0.37) and non-infusion adverse events (68.3% vs. 71.2%, p = 0.47) were also similar in the two groups, with a survival curve demonstrating no difference between the two products and data analysis meeting the non-inferiority criteria. Conclusions: Rituximab and rituximab-abbs are non-inferior to each other in both efficacy and safety. Long term follow up would be needed to confirm these results.