Introduction: In Cuba, Primary Immunodeficiencies (PID) patients have been diagnosed since 1966. In September 2004, we started a multi-center project with the participation of the different provinces of the country for the registration of PID patients in Cuba. This constitutes the four report and includes all live patients diagnosed at the time until June/2022. Methods:The criteria for the phenotypic diagnoses of PID in this project were taken of Latin American Society Immunodeficiency Diseases (LASID) and it includes all diagnoses used by the World Health Organization (WHO) and the European Registry for Immunodeficiency Diseases (ESID) and the most recent classification developed by the International Union of Immunological Societies (IUIS) PID Classification Committee. Pediatric and adult-made clinical histories were used for project purposes that record the variables: demographic information, clinical and phenotypic characteristics, molecular defect, inheritance, associated diseases, nutritional status, quality of life, form of presentation, types of infections and laboratory tests used for diagnosis and treatment. Results: A total of 410 patients with PID have been registered. Antibody immunodeficiencies were the most frequent (n=200;48,7%) and within them, selective IgA deficiency prevailed (n=132; 66%), following in frequency the combined IDs (n=74;18%) those associated with phagocyte defects (n=50;12,1%),complement deficiencies(n=44;10,7%) with predominance of Familial hereditary angioedema (C1 esterase inhibitor deficiency, n=42), well-defined syndromes (n=24;5,8%), followed by autoinflammatory syndromes (n=8;1,9%) and defects of innate immunity (n=6;1.4%). Conclusions: Our results allow us to update the frequency of PID in Cuba,an earlier diagnosis, the introduction of subcutaneous IgG treatment (gammanorm,Octapharma) and Gamma Interferon with excellent results, better quality of life, identify the associated pathological alterations and to promote clinical research through a diagnostic network in our country. The largest number of patients corresponds to the province of Havana, due to having a greater number of medical consultations and greater resources for diagnosis.