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Mechanical ventilation (MV) is the most common therapeutic modality used for critically ill patients. However, prolonged MV is associated with high morbidity and mortality. Therefore, it is important to avoid both premature extubation and unnecessary prolongation of MV. Although some studies have determined the predictors of early weaning success and failure, only a few have investigated these factors in critically ill surgical patients who require postoperative MV. The aim of this study was to evaluate predictors of early weaning failure from MV in critically ill patients who had undergone emergency gastrointestinal (GI) surgery.The medical records of 3327 adult patients who underwent emergency GI surgery between January 2007 and December 2016 were reviewed retrospectively. Clinical and laboratory parameters before surgery and within 2 days postsurgery were investigated.This study included 387 adult patients who required postoperative MV. A low platelet count (adjusted odds ratio [OR]: 0.995; 95% confidence interval [CI]: 0.991–1.000; P = .03), an elevated delta neutrophil index (DNI; adjusted OR: 1.025; 95% CI: 1.005–1.046; P = .016), a delayed spontaneous breathing trial (SBT; adjusted OR: 14.152; 95% CI: 6.571–30.483; P < .001), and the presence of postoperative shock (adjusted OR: 2.436; 95% CI: 1.138–5.216; P = .022) were shown to predict early weaning failure from MV in the study population.Delayed SBT, a low platelet count, an elevated DNI, and the presence of postoperative shock are independent predictors of early weaning failure from MV in critically ill patients after emergency GI surgery.