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OBJECTIVE: Blood donation in Brazil is marked by a turbulent history of decentralized hemotherapy, without efficient policies. Article 64 of Federal Law No. 10,205/2001 requires that, prior to donation, candidates undergo a confidential screening process. This step is subdivided into: registration, and clinical and serological screening. Subsequently, the donor is considered fit, or as presenting permanent or temporary unfitness. Thus, the objective was to compare the main causes of unfitness to donate blood among men and women from blood centers between 2017 and 2020. METHODS: Observational and retrospective study, with a quantitative and qualitative approach. Tabulated information for the years 2017 to 2020 was extracted from the hemocenter database. RESULTS: Analysis was performed by comparing the causes of unfitness, in this case the sum between men and women, between the years 2017 and 2020. Among the 5 causes of unfitness for men, 4 are repeated every year, namely: use of medication, self-medication, and/or effective need for chronic diseases; recent surgery; risky sexual intercourse; arterial hypertension. Among the 5 causes of disability for women, 4 are repeated every year: medication use; recent surgery; low hematocrit/hemoglobin; tattoo/acupuncture/ear lobe piercing. CONCLUSION: When listing the main exclusion factors for donation between the sexes, it is noticeable that the causes remain constant over the years.