Objective: Immunoglobulin replacement is standard therapy that prevents/controls infectious complications caused by primary immunodeficiency disorders especially common variable immunodeficiency and X-linked agammaglobulinemia. In Canada, the therapy is administered intravenously (IVIg) at hospital, whereas in some European countries it is administered subcutaneously (SCIg) at home and intravenously at home/hospital. Canadian Blood Service is considering establishing SCIg as an alternative to IVIg. Concerns over increasing healthcare costs raise questions about its cost-effectiveness. The present study is intended to estimate cost effectiveness of SCIg against hospital-IVIg and hypothetical home-IVIg from Canada's public healthcare payer perspective. Methods: A Markov decision-analytical model for hypothetical patients in 12-month therapy was used to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) for SCIg compared with hospital-IVIg and home-IVIg. Serious adverse events, mortality, number and severity of infections were considered. Results: SCIg dominates (greater benefits at lesser costs) hospital-IVIg and produces an incremental cost effectiveness ratio (ICER) of CND$39,500/QALY when compared to home-IVIg. ICER is sensitive to changes in utility of infection, hospital charges, and infusion materials Conclusion: SCIg appears to be the most cost-effective intervention if decision makers are willing to pay CND$39,500/QALY. Therefore, it could be gradually established as an alternative to patients who are willing and clinically suitable to switch. Uncertainty in the available comparative clinical effectiveness warrants a reliable comparative clinical study.