The subcutaneous immune globulin (SCIG) 20% product, Ig20Gly, was shown to be efficacious and well tolerated in 2 phase 2/3 North American and European studies at infusion volumes up to 60 mL/site and rates up to 60 mL/h/site in patients with primary immunodeficiency diseases. To assess patient experience after switching to Ig20Gly with fast infusion rates and large infusion volumes/site in the North American study. In this analysis of the open-label phase 2/3 study in which patients aged ≥2 years received weekly Ig20Gly infusions for up to approximately 1.3 years, tolerability and infusion parameters were assessed throughout the study for all patients and by prestudy treatment regimen (intravenous [IV] switchers or SC switchers). Overall, 61% of patients reached the infusion rate of ≥60 mL/h/site and continued at this rate for 1 or more subsequent infusions; the median infusion number when patients first reached ≥60 mL/h/site was 3. No association was found between higher infusion volumes or rates and increased incidences of local and systemic adverse events (AEs) in the total population and patients younger than 16 years. Infusion parameters and tolerability were generally comparable regardless of the route of prestudy treatment (IV or SC switchers); however, IV switchers experienced lower rates of local AEs than SC switchers and had a slightly higher median infusion volume per site and longer infusion duration vs SC switchers. High Ig20Gly infusion rates of at least 60 mL/h/site and volumes ≥60 mL/site were well tolerated during onboarding and throughout treatment, regardless of prestudy treatment. ClinicalTrials.gov Identifier NCT01218438.