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Background: Primary (PID) or secondary (SID) immunodeficiencies are diseases caused by quantitative and/or functional alterations of the different mechanisms involved in the innate and adaptive immune response. This economic evaluation was conducted to compare the cost of treatment of HYQVIA® (hyaluronidase-facilitated subcutaneous infusion of immunoglobulin, fSCIG) compared to intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG), currently reimbursed in Italy, in the treatment of PIDs or SIDs. Methods: A cost-minimisation analysis was carried out, considering the hospital’s perspective. The direct medical costs (cost of immunoglobulins and cost of administration) were assessed. The analysis was conducted considering one year (52 weeks) time horizon. The reference population included adult patients with PID with impaired antibody production or adult patients with SID with severe or recurrent infections, ineffective antimicrobial treatment and documented specific antibody defect (PSAF) or serum IgG level < 4 g/L. Results: In the maintenance treatment of PID, HYQVIA® (€ 20,020.00) was the therapeutic alternative with the lowest mean annual cost compared to HIZENTRA® (€ 22,165.19) and VENITAL® (€ 24,967.68). Moreover, in the maintenance treatment of SIDs, HYQVIA® (€ 17,160.00) was the cost-saving therapeutic alternative compared to VENITAL® (€ 22,107.68). A sensitivity analysis confirmed the base case results. Conclusion: Due to lower costs of administration and different scheme of administration, HYQVIA® was a cost-saving alternative to SCIG e IVIG in the treatment of PID and to IVIG in the treatment of SID