Background: Randomized studies reported a marginal superiority of polyclonal antithymocyte globulins (ATG, Thymoglobulin®, Sanofi, Gentilly, France, or Fresenius®, Bad Homburg, Germany) to prevent acute rejection compared to monoclonal anti-CD25 antibodies (IL2Ra). Nevertheless, the representativeness and the generalizability of these studies are questionable. Methods: We studied the impact of ATG use in real-life conditions in a multicenter study. Propensity score analysis was performed to address potential confounding by indication. Results: 817 patients were included. Logistic regression revealed that age, male gender, a pre-transplant history of cancer, presence of anti-HLA antibodies, previous kidney transplantation, and transplant center were associated with ATG use. The area under the curve of the propensity score was 0.84 + 0.02. ATG use was not associated with a lower rate of acute rejection (18.2% in ATG-treated patients vs 15.8% in non-ATG-treated patients, p =0.356). Adjustment for propensity score slightly modified the relationship between ATG and acute rejection towards a more neutral effect ( p =0.913). Score match analysis recapitulated the previous result. ATG use was associated with the occurrence of opportunistic infection ( p =0.034). There was no difference in graft loss or death between the two groups. Conclusions: In real-life conditions, ATG does not substantially reduce the risk of acute rejection after kidney transplantation. A better discrimination of patients who may benefit from ATG is required.