The lifelong IgG replacement therapy for patients with primary immunedeficiencies (PIDD) may be provided by intravenous (IVIG) or by subcutaneous IgG (SCIG) infusions. We investigated the impact of weekly SCIG self-infusions at home on the health-related quality of life, treatment satisfaction, and preferences in patients treated with IVIG at the hospital/doctor's office (Group A) or at home (Group B) before the study started. Forty-four adult North American PIDD patients were included in the study, 28 patients in Group A and 16 in Group B. Patients in Group A reported significantly less limitations with their work/daily activities, a significantly improved vitality, and better general health. Treatment satisfaction was significantly improved in Group A. The preference for the subcutaneous route and for home therapy was respectively 81% and 90% in Group A. In Group B, 69% preferred the subcutaneous route and 92% home therapy.