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Background To investigate the risk factors for early acute gastrointestinal injury (AGI) in critically ill patients admitted to the intensive care unit (ICU).Methods A total of 753 ICU patients from 2008 to 2022 selected from the MIMIC database were included in this study. Based on the occurrence of AGI within the first week of admission, patients were divided into two groups: the AGI group (observation group, n=351) and the non-AGI group (control group, n=402). Univariate analysis was performed on various clinical parameters from both groups. Indicators showing statistically significant differences in the univariate analysis were then included as independent variables in a multivariate logistic regression analysis to identify risk factors for early AGI. The predictive value of these risk factors was assessed using receiver operating characteristic (ROC) curve analysis.Results The neutrophil-to-lymphocyte ratio (NLR), lactate level, albumin level, and duration of vasoactive drug use in the observation group were 12.17 ± 3.1, 5.6 ± 1.3 mmol/L, 27.3 ± 4.3 g/L, and 68 (0, 77.5) hours, respectively. Corresponding values in the control group were 9.8 ± 2.6, 3.1 ± 1.20 mmol/L, 27.2 ± 3.1 g/L, and 0 (0, 38) hours. All differences between the groups were statistically significant (P < 0.05). Multivariate logistic regression analysis identified NLR (OR=1.24, 95% CI: 1.18–1.3, P < 0.001), lactate level (OR=2.54, 95% CI: 1.28–3.8, P=0.001), and duration of vasoactive drug use (OR=1.05, 95% CI: 1.01–1.09, P < 0.001) as independent risk factors for early AGI. Albumin level was identified as a protective factor (OR=0.77, 95% CI: 0.63–0.81, P=0.001). ROC curve analysis showed that the area under the curve (AUC) for NLR, lactate, and duration of vasoactive drug use were 0.800 (95% CI: 0.707–0.894), 0.969 (95% CI: 0.940–0.999), and 0.716 (95% CI: 0.600–0.831), respectively, with corresponding sensitivities of 65%, 85%, and 55%, and specificities of 80%, 95%, and 88%. All differences were statistically significant (P < 0.05).Conclusions Elevated NLR, increased lactate levels, and prolonged use of vasoactive drugs are significant risk factors for early AGI in critically ill ICU patients. The combination of these indicators demonstrates considerable predictive value for the early development of AGI.