Introduction: Currently, routine screening for HIV, hepatitis B and C and syphilis is done in most blood banks in the world. Methods: We conducted a prospective descriptive study at the National Blood Transfusion Center (CNTS) Antananarivo for a period of 7 months from January to July 2014, which aims to assess the socio-clinical factors accompanying ineligibility of blood products and to determine the seroprevalence of HIV, hepatitis B, C and syphilis of the blood donors who have spent at CNTS HU – JRA Antananarivo during this period. All donors who have abnormal results of microbiological examinations were included. The parameters used and studied were age, sex, marital status, blood and results microbiological examinations for HIV, hepatitis B, C, and syphilis. The prevalence of blood donors who presented a serological abnormality is 3.95% with a predominance of donors with hepatitis B (72.93%) followed by syphilis (18.29%) of the hepatitis C (6.95%) and HIV (1.80%) and a predominance of young people. Conclusion: At the CNTS Antananarivo, the HBV is the main definitive reason for exclusion of these donors. This high prevalence is a real public health problem for the country’s health authorities. The search for maximum safety in blood transfusion through firstly a better selection of blood donors by implementing a policy of strong loyalty and other early diagnosis of major diseases transmissible by blood and likely to infect the recipient.