BACKGROUND: Assessing the risk of hemolytic uremic syndrome (HUS) during Escherichia coli O157 infection due to antibiotic treatment is crucial for identifying the potential risks associated with antibiotic use. This study aimed to analyze the factors influencing the development of HUS. METHODS: Three databases were searched. The search was conducted between October and November 2024, and included studies up to November 2024. The primary outcome was the development of HUS in E. coli O157 infection with or without antibiotic treatment; pooled estimates of odds ratios [OR] and 95% confidence interval [CI] were obtained using random-effects models if there was evidence of heterogeneity (RevMan 5.4.1). RESULTS: Twenty-three studies with 17,975 patients were included. An increased risk of HUS was found when analysing treatment with any type of antibiotic (OR 1.47; 95% CI 1.03-2.09). Among the different antibiotic families analysed, β-lactams significantly increased the risk of developing HUS in E. coli O157 infections (OR 2.37; 95% CI 1.79-3.15). The use of fosfomycin resulted in a decreased incidence of HUS (OR 0.56; 95% CI 0.40-0.77). CONCLUSION: Antibiotic therapy slightly increased the risk of progression to HUS in E. coli O157 infection. The use of β-lactams seems to increase this risk, whereas fosfomycin appears to have a protective role against this infection.