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Background: Glycemic variability (GV) is a prevalent and significant condition observed in critically ill patients. This study aimed to investigate the relationship between early glycemic variability parameters and 28-day mortality in critically ill patients. Methods: A multicenter, prospective, and observational study was performed at five tertiary intensive care units (ICUs) in Turkey. All patients who had more than six blood glucose level (BGL) measures per 24 h were included. The parameters of GV including the SD, MGL, MGD (the difference between the maximal and minimal glucose level), and the CV (the percentage of SD to the MGL) in the first 24 h were recorded. Results: A total of 578 eligible patients were enrolled in the study, of whom 43.6% were women. The mean age of the patients was 68.09 ± 16.62 years. Overall mortality was 31.5% (n = 182). The glycemic parameters of the CV, SD, and MGD were significantly higher in the non-survivor group than in the survivor group (p = 0.040, 0.006, and 0.002, respectively). The multivariate logistic regression analysis revealed that the CV (OR 1.023; 95% CI 1.004–1.042; p = 0.017) was an independent factor that increased mortality. Spearman's rho correlation analysis revealed a strong (r:0.871) and statistically significant correlation (p < 0.001) between the CV and MGD. Conclusions: The CV calculated within the first 24 h of ICU admission is independently associated with 28-day mortality. The MGD is correlated with the CV and is maybe a practical tool to predict increased risk of mortality at the bedside. However, further studies are needed to establish the independent association of the MGD with mortality. [ABSTRACT FROM AUTHOR]