PURPOSE: To evaluate mortality risk factors in pediatric-onset common variable immunodeficiency disorders (CVID), we evaluated the largest single-institution cohort of pediatric-onset CVID patients. Previous publications on CVID have provided valuable descriptive data, but lack risk stratification to guide physicians in management of these patients. METHODS: Retrospective chart review of 198 subjects with CVID at a single institution, of whom 91 had disease onset at a pediatric age. Clinical and laboratory data were collected at diagnosis and in follow-up. Odds ratios and Fisher tests were utilized to examine trends. This study was approved by an institutional review board. RESULTS: Clinical features and laboratory results for subjects diagnosed with CVID at a pediatric age are similar to those who had adult-onset CVID. However, majority of the deceased subjects (13/18) were at a pediatric age at CVID symptom onset. These subjects had a lower age at mortality, multiple comorbidities, and often depression. The most common cause of death was infection. Lung disease (OR 5, p < 0.05) and infection with severe/opportunistic organisms (OR 9, p < 0.05) are directly related to increased mortality. Delay in diagnosis of CVID is also correlated with mortality. Intermediary markers correlating with mortality include anemia, GERD, and depression. CONCLUSIONS: There are many similarities between patients with pediatric- and adult-onset CVID; however, the mortality of pediatric CVID in our cohort is striking. This is the first study to identify specific factors correlated with mortality in pediatric-onset CVID to guide pediatricians and subspecialists in managing these immunodeficient patients.