We evaluated 131 children (M = 88, F = 43) with hypogammaglobulinemia. Data was analyzed mainly for delineating predictor factors for outcome. The distance from the lower limit of normal (− 2SD) for any single measurement of immunoglobulins (Ig) was calculated and transformed into Ig scores. Mean age and duration of follow-up were 5.06 ± 4.05 and 3.7 ± 3.03 years, respectively. The diagnoses were: 22 CVID, 16 IgA deficiency, 33 transient hypogammaglobulinemia of childhood (THC), 3 selective IgM deficiency and 57 unclassified hypogammaglobulinemia (UCH). Low IgA scores (<−0.124) at presentation were indicative of subsequent development of IgA deficiency or CVID, whereas low IgM score (<−0.038) pointed towards more severe and persistent phenotypes. Combination of low IgM score between 2 and 5 years, impaired antibody response and low B cell counts enabled us to predict persistence of hypogammaglobulinemia beyond 5 years (specificity = 90.5% and PPV = 94.9%) and chronic lung disease (sensitivity = 90.4% and specificity = 68.3%). The set of criteria including low IgM scores, impaired antibody response and low B cell counts provided a high predictive value in detecting those with persistent hypogammaglobulinemia.