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Abstract Background and Aims hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) represent the major transfusion–transmissible pathogens worldwide. The risk of transmission is relatively high in African countries, mainly due to unreliable screening methods of blood donations. In Burkina Faso, predonation screening using rapid diagnostic tests (RDTs) is widespread, raising the major question of the transfusion safety in the country. The objective of this study was to assess the risk of transmission of HBV, HCV, and HIV through blood transfusion in the context of the use of RDTs for screening of the blood donations. Methods In this cross‐sectional study, a total of 417 serum samples obtained from blood donors tested negative for HBsAg, anti‐HCV, and anti‐HIV using RDTs were retested for the same markers using chemiluminescent immunologic assays. Total antibodies to HBV core (anti‐HBc) were tested on randomly selected samples. HBV‐DNA and HCV‐RNA viral loads (VLs) were quantified on HBsAg and anti‐HCV positive samples, respectively. To assess possible occult hepatitis B infection (OBI), HBV‐DNA‐VL was quantified on 313 randomly selected HBsAg‐negative samples. Results HBsAg and anti‐HCV were found respectively in 6 (6/417; 1.4%) and 11 (11/417; 2.6%) samples. No samples were reactive for anti‐HIV. Total anti‐HBc were detected in 217 out of the 319 randomly selected samples (217/319; 68.02%). HBV‐DNA was detected in four (4/313; 1.27%) samples, including two (2/6; 33.33%) of the six HBsAg positive samples and two (2/313; 0.6%) of the HBsAg‐negative samples, suggesting two cases of occult HBV infection. All anti‐HCV antibody‐positive samples were HCV‐RNA negative. Conclusion This study shows that RDTs are not sufficiently sensitive for the screening of blood donations. Our results highlight the urgent need to think about the extension of sensitive immunological tests in all blood transfusion centers and also the implementation of nucleic acid amplification techniques.