Infection is a cause of death in solid organ transplantation. Secondary antibody deficiency is a risk factor of severe infection in solid organ transplantation. In a multicenter randomized clinical trial we evaluated the efficacy and safety of an intravenous immunoglobulin (IVIG) protocol to decrease the rate of re-infection in solid organ recipients with severe infections and secondary antibody deficiency. Adult patients (20 Heart, 12 Lung, 5 Kidney, 3 Liver Recipients) with post transplant severe infections and secondary antibody deficiency (IgG levels < 600 mg/dL at the time of the infectious complication) were included. IVIG protocol: Two doses of 15 grams followed by other 3 doses of 20 grams of a 5% IVIG product. 40 patients were randomized to receive IVIG in combination with conventional antimicrobial therapy (n=20) or conventional antimicrobial therapy alone (n=20). At the time of this preliminary report 36 patients that completed the protocol were analysed (17 IVIG + antimicrobial therapy, 19 antimicrobial therapy alone). Distinct specific antibodies were tested at the time of inclusion in the clinical trial and at the time of final visit (visit 7 at 30-45 days after last IVIG dose or similar time in no-IVIG patients) in a subgroup of patients to assess the kinetics of humoral immunity reconstitution. The primary outcome measure (rate of re-infection) was significantly lower in patients randomized to receive IVIG as compared with patients receiving only conventional antimicrobial therapy (35.3 vs 68.4%, chi-square test, p=0.047). Time to reach normal IgG (IgG > 750 mg/dL) was shorter in IVIG group (55±44 vs 93±42 days, p=0.06). Significantly higher levels of specific anti-cytomegalovirus, anti-clostridium difficile toxins A and B was demonstrated at visit 7 in patients who received IVIG as compared with patients that were treated with antimicrobial therapy alone. In a randomized clinical trial we have preliminarily demonstrated that IVIG is associated with reconstitution of distinct specific antibodies and with a lower rate of re-infection in solid organ transplantation with severe infection and secondary antibody deficiency.