OBJECTIVES: Intravenous immunoglobulin (IGIV) made from chromatography-caprylate methods (IGIV-C, 10%) was associated with a reduction in validated infections (pneumonia, sinusitis and acute exacerbation of chronic sinusitis) when compared to IGIV made from solvent-detergent methods (IGIV-SD, 10%) in patients with primary immunodeficiency disease. Our objective was to determine the cost-effectiveness of IGIV-C. METHODS: We performed a retrospective economic analysis of a double-blind, randomized, clinical trial. Participants were randomly assigned to IGIV-C (n = 87) or IGIV-SD (n = 85) and monitored for the development of validated infections over the course of 9 months. Consumed resources were enumerated including cost of physician and emergency room visits, medications (prescription and over-the-counter), work productivity losses and hospitalizations. Resource data was obtained from case report forms, patient diaries and the trial medication database. Unit costs were obtained from national costing sources (Thomson's Redbook, Health Care Utilization Project database), etc. Pricing of both IGIV products was the same therefore IGIV acquisition costs were not included in the analyses. We used a societal perspective with indirect costs, measured in 2003 U.S. dollars. RESULTS: In a multivariate analysis, mean per participant costs were significantly lower between those receiving IGIV-C compared to IGIV-SD for prescription medications (-$302, 95% CI: -$598, -$6), hospitalization (-$1454, 95% CI: -$1828, -$1080) and total costs (-$1304, 95% CI: -$1867, -$742). Participant costs associated with lost work productivity and physician visits were similar for both groups (p > 0.10). In sensitivity analyses, using 80% of average wholesale price for costing prescription medications instead of 95%, the mean per participant costs remained statistically lower for the IGIV-C group. CONCLUSIONS: IGIV-C is cost-saving and provides incremental health benefits therefore it is a dominant strategy compared to IGIV-SD. Differences in the process of immunoglobulin manufacturing can lead to meaningful clinical and economic outcome differences in the care.