Background: Massive transfusions are associated with a high mortality rate, but there is little evidence indicating when such efforts are futile. The purpose of this study was to identify clinical variables that could be used as futility indicators in massively transfused patients. Methods: We retrospectively analyzed 138 adult surgical patients at our institution receiving a massive transfusion (2016)(2017)(2018)(2019). Peak lactate and nadir pH within 24 h of massive transfusion initiation, along with other clinical variables, were assessed as predictors of the primary outcome, in-hospital mortality. Results:The overall rate of in-hospital mortality among our patient population was 52.9% (n = 73). Increasing lactate and decreasing pH were associated with greater mortality among massively transfused patients. Mortality rates were~2-fold higher for patients in the highest lactate category (≥10.0 mmol/L: 25 of 37; 67.6%) compared to the lowest category (0.0-4.9 mmol/L: 17 of 48; 35.4%) (p = .005), and~2.5-fold higher for patients in the lowest pH category (<7.00: 8 of 9; 88.9%) compared to the highest category (≥7.40: 8 of 23; 34.7%) (p = .016). Increasing age was also associated with higher mortality (≥65 years: 24 of 33; 72.7%) when compared to younger patients (18-64 years: 49 of 105; 46.7%) (p = .010).Conclusions: Peak lactate ≥10.0 mmol/L, nadir pH <7.00, and age ≥65 years were significantly associated with higher rates of in-hospital mortality among massively transfused patients. Incorporating these clinical parameters into a futility index for massive transfusions will be useful in situations where blood products are scarce and/or mortality may be unavoidable.