Hypogammaglobulinemia (serum immunoglobulin G (IgG) levels < 7.0 g/L) has been associated with increased risk of COPD exacerbations but has not yet been shown to predict hospitalizations.To determine the relationship between hypogammaglobulinemia and the risk of hospitalization in patients with COPD.and methods: Serum IgG levels were measured on baseline samples from four COPD cohorts (n=2,259): Azithromycin for Prevention of AECOPD (MACRO, n=976); Simvastatin in the Prevention of AECOPD (STATCOPE, n=653), Long-Term Oxygen Treatment Trial (LOTT, n=354), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE, n=276). IgG levels were determined by immunonephelometry (MACRO; STATCOPE) or mass spectrometry (LOTT; CASCADE). The effect of hypogammaglobulinemia on COPD hospitalization risk was evaluated using cumulative incidence functions for this outcome and deaths (competing risk). Fine-Gray models were performed to obtain adjusted subdistribution hazard ratios (SHR) related to IgG levels for each study and then combined using a meta-analysis. Rates of COPD hospitalizations per person-year were compared according to IgG status.The overall frequency of hypogammaglobulinemia was 28.4%. Higher incidence estimates of COPD hospitalizations were observed among participants with low IgG levels compared to those with normal levels (Gray's test, P < .001); pooled SHR (meta-analysis) was 1.29 (95% CI: 1.06 - 1.56, P = .01). Among patients with prior COPD admissions (n=757), the pooled SHR increased to 1.58 (95% CI: 1.20 - 2.07, P < .01). The risk of COPD admissions, however, was similar between IgG groups in patients with no prior hospitalizations: pooled SHR = 1.15 (95% CI: 0.86 - 1.52, P =.34). The hypogammaglobulinemia group also showed significantly higher rates of COPD hospitalizations per person-year: 0.48 ± 2.01 vs. 0.29 ± 0.83, P < .001.Hypogammaglobulinemia is associated with a higher risk of COPD hospital admissions.