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Background: Immunodeficiency is a heterogenous group of diseases affecting different components of the immune system. Patterns of infection, etiology and organ involvement are not similar in this risky population. This study was conducted to determine the prevalence of congenital and acquiring immunodeficiencies and also recognizing the most common infections and affected organs. Materials and Methods: In a retrospective, cross-sectional survey, during 2006-2012, we reviewed all hospital records with any kind of immunodeficiency admitted in, all departments of university referral hospital, Isfahan, Iran. Results: Various immunodeficiencies, sorted by prevalence, were as below: Primary immunodeficiency diseases (PIDs) 122 (27.4%), lymphohematogenous malignancy (LHM) 105 (23.5%), solid cancer 56 (12.6%), human immunodeficiency virus/acquired immunodeficiency syndrome 64 (14.5%), non-cytotoxic immunosuppresion 94 (21%), and splenectomy 5 (1.2%). Common sources of infection were blood, lungs and buccal cavity. Conclusion: The most frequent type of immunodeficiency was PIDs and LHM. Infection continues to be a major problem in all variety of immunodeficiency.