<h3>Objective:</h3> To compare the efficacy of strategies to manage hypogammaglobulinemia in neuroimmunology patients on anti-CD20 agents, including the effect of anti-CD20 dose reduction and reduced dosing frequency, IVIG/SCIG, anti-CD20 cessation, and DMT switches. <h3>Background:</h3> Anti-CD20 monoclonal agents are increasingly used as therapies for multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Few studies have compared strategies to address hypogammaglobulinemia. <h3>Design/Methods:</h3> All MS, NMOSD, and MOGAD patients at our institution with hypogammaglobulinemia on anti-CD20 agents from 2001–2022 were analyzed. The median change in IgG, infection frequency, and infection severity before and after the treatment was calculated. <h3>Results:</h3> In total, 257 patients were screened, and 30 had a treatment for hypogammaglobulinemia. IVIG/SCIG yielded the largest increase in IgG per year (674.0 mg/dL), followed by B-cell therapy cessation (34.7 mg/dL), and DMT switch (5.9 mg/dL). Dose reduction had the largest decrease in yearly infection frequency (2.7 fewer infections), followed by IVIG/SCIG (2.5 fewer), DMT switch (2 fewer), and reduced dosing frequency (0.5 fewer). Infection grade decreased by 1.9 for reduced dosing frequency (less severe infections), by 1.3 for IVIG/SCIG, and by 0.6 for DMT switch. <h3>Conclusions:</h3> This data suggests that IVIG/SCIG may yield the greatest recovery in IgG while also reducing infection frequency and severity. Stopping anti-CD20 therapy and/or switching DMTs also increase IgG and may lower infection risk. Overall, longer follow-up is needed to assess IgG recovery and infection risk with these interventions. <b>Disclosure:</b> Ms. Kelly has nothing to disclose. The institution of Dr. Vishnevetsky has received research support from National MS Society. The institution of Dr. Vishnevetsky has received research support from NIH (NeuroNext). Lori B. Chibnik has nothing to disclose. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Pharma. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Levy has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Various law firms. The institution of Dr. Levy has received research support from National Institutes Health.