The demographics, immunologic parameters, medical complications, and mortality statistics from 473 subjects with common variable immune deficiency followed over 4 decades in New York were analyzed. Median immunoglobulin levels were IgG, 246 mg/dL; IgA, 8 mg/dL; and IgM, 21 mg/dL; 22.6% had an IgG less than 100 mg/dL. Males were diagnosed earlier (median age, 30 years) than females (median age, 33.5 years; P = .004). Ninety-four percent of patients had a history of infections; 68% also had noninfectious complications: hematologic or organ-specific autoimmunity, 28.6%; chronic lung disease, 28.5%; bronchiectasis, 11.2%; gastrointestinal inflammatory disease, 15.4%; malabsorption, 5.9%; granulomatous disease, 9.7%; liver diseases and hepatitis, 9.1%; lymphoma, 8.2%; or other cancers, 7.0%. Females had higher baseline serum IgM (P = .009) and were more likely to develop lymphoma (P = .04); 19.6% of patients died, a significantly shorter survival than age- and sex-matched population controls (P < .0001). Reduced survival was associated with age at diagnosis, lower baseline IgG, higher IgM, and fewer peripheral B cells. The risk of death was 11 times higher for patients with noninfectious complications (hazard ratio = 10.95; P < .0001). Mortality was associated with lymphoma, any form of hepatitis, functional or structural lung impairment, and gastrointestinal disease with or without malabsorption, but not with bronchiectasis, autoimmunity, other cancers, granulomatous disease, or previous splenectomy.