The aim of this study is to compare clinical and cost outcomes of patients undergoing subcutaneous immunoglobulin (SCIG) therapy who were managed by a clinical management program to the matched controls in the United States. Methods: This was a retrospective cohort study using administrative claims data from the PharMetrics Plus™ (PMTX+) database. The patients from a high-touch SCIG clinical management program were matched to nonprogram patients in PMTX+ database using 1:4 propensity score matching without replacement. All patients were followed for 1 year during the study from September 1, 2011, to June 30, 2014, and both clinical and cost outcomes were compared between the two cohorts using the generalized estimating equation model. Findings: The clinical outcomes were measured by infection- and infusion-related adverse events (AEs). Most of them were not significantly different (P > 0.05) between the intervention group and matched controls. Although the proportion of patients who had a mild less common AE was higher (4.4% vs. 0.0%;P = 0.04), it could be due to increased reporting among the intervention group. The annual adjusted mean total health-care costs of patients in the program (n = 45) were $20,868 lower compared to matched controls (n = 180), representing a 24% lower costs ($66,450 vs. $87,318;P = 0.009). Conclusion: This study may demonstrate that clinical management programs for SCIG may be associated with lower health-care costs and comparable infection and severe AE rates. The limitations of this study included a small sample size and a reliance on administrative claim data.