Background: Blinatumomab has demonstrated efficacy in minimal residual disease (MRD) positive and relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) by inciting rapid and sustained B-cell depletion. Methods: Owing to its effect on B-cells, blinatumomab is associated with a higher rate of secondary hypogammaglobulinemia compared to chemotherapy. To mitigate blinatumomab-induced hypogammaglobulinemia, patients were pre-emptively repleted with intravenous immune globulin (IVIG) during blinatumomab therapy. In this retrospective study, we compared outcomes of 23 blinatumomab treated adults with ALL. Seventeen patients routinely received IVIG and 6 patients were in the control cohort. Results: Our findings demonstrated no difference between the two cohorts in immunoglobulin G (IgG) nadir (338 mg/dL vs. 337 mg/dL, P =0.641), days to IgG nadir (120.5 vs. 85.5 days, P =0.13), infection rate (82.4% vs. 66.7%, P =0.58), infections requiring ICU admission (23.5% vs. 16.7%, P =1), and infection related mortality (17.6% vs. 16.7%, P =1). Conclusion Pre-emptive IVIG repletion during blinatumomab did not prevent hypogammaglobulinemia and associated infection risk.