Objective: The present study aimed to verify the efficacy of calcium ions as a prognostic factor for massive transfusion (MT) in patients with upper gastrointestinal bleeding (UGIB), including those of variceal and non-variceal origin. Methods: This retrospective cohort study included adult patients with acute UGIB hospitalized through the prehospital emergency department between January 2018 and December 2022. The primary outcome was the need for MT. Secondary outcomes comprised hospital mortality, the need for angiographic intervention or surgery, length of hospital stay, and length of intensive care unit stay. Multivariate analysis using logistic regression was performed for possible candidates and included ionized calcium levels for predicting MT. Results: According to the multivariate logistic regression assessment, the primary outcome was independently correlated with hemoglobin (odds ratio [OR]=0.702; 95% confidence interval [CI], 0.554-0.889) and ionized calcium levels (OR=0.009; 95% CI, 0.0002-0.469). The optimal cutoff point for ionized calcium levels was determined to be a value of 1.105, with a sensitivity of 0.88 and a specificity of 0.488. Using this value, the lower ionized calcium group needed a nearly six-fold increase in MT compared to the upper group. However, the secondary outcomes did not show any statistical differences. Conclusion The statistical review in the present study indicates that low ionized calcium levels in UGIB patients, regardless of liver cirrhosis as a comorbidity, are a novel independent prognostic factor for MT. Quick measurement of ionized calcium levels using a blood gas analyzer will enable practitioners to rapidly identify UGIB patients who need urgent care in minutes.