Purpose: A high anion gap (AG) is known to be a significant risk factor for serious acid-base imbalances and death in acute poisoning cases. The strong ion difference (SID), or strong ion gap (SIG), has recently been used to predict in-hospital mortality or acute kidney injury (AKI) in patients with systemic inflammatory response syndrome. This study presents a comprehensive acidbase analysis in order to identify the predictive value of the SIG for disease severity in severe poisoning. Methods: A cross-sectional observational study was conducted on acute poisoning patients treated in the emergency intensive care unit (ICU) between December 2015 and November 2020. Initial serum electrolytes, base deficit (BD), AG, SIG, and laboratory parameters were concurrently measured upon hospital arrival and were subsequently used along with Stewart’s approach to acid-base analysis to predict AKI development and in-hospital death. The area under the receiver operating characteristic curve (AUC) and logistic regression analysis were used as statistical tests. Results: Overall, 343 patients who were treated in the intensive care unit were enrolled. The initial levels of lactate, AG, and BD were significantly higher in the AKI group (n=62). Both effective SID [SIDe] (20.3 vs. 26.4 mEq/L, p<0.001) and SIG (20.2 vs. 16.5 mEq/L, p<0.001) were significantly higher in the AKI group; however, the AUC of serum SIDe was 0.842 (95% confidence interval [CI]=0.799-0.879). Serum SIDe had a higher predictive capacity for AKI than initial creatinine (AUC=0.796, 95% CI=0.749-0.837), BD (AUC=0.761, 95% CI=0.712-0.805), and AG (AUC=0.660, 95% CI=0.607-0.711). Multivariate logistic regression analyses revealed that diabetes, lactic acidosis, high SIG, and low SIDe were significant risk factors for in-hospital mortality. Conclusion: Initial SIDe and SIG were identified as useful predictors of AKI and in-hospital mortality in intoxicated patients who were critically ill. Further research is necessary to evaluate the physiological nature of the toxicant or unmeasured anions in such patients.