The relationship between acidosis and coagulopathy has long been described in vitro and in trauma patients, but not yet in orthotopic liver transplantation (OLT). The association of metabolic acidosis with coagulopathy and with transfusion requirements was evaluated in patients submitted to OLT. Changes in acid-base and coagulation parameters were analyzed by repeated measures. Regression analyses [adjusted for sex, age, model for end stage liver disease (MELD) score, and baseline values of hemoglobin, fibrinogen, international normalized ratio, platelets] determined the association of acid-base parameters with coagulation markers and transfusion requirement. We included 95 patients, 66% were male, 49.5% of the patients had hepatocellular carcinoma and the mean MELD score was 20.4 (SD 8.9). The values of all the coagulation and acid-base parameters significantly changed during OLT, particularly in the reperfusion phase. After adjustments for baseline parameters, the decrease in pH and base excess (BE) values were associated with a decrease in fibrinogen levels (mean decrease of fibrinogen level = 14.88 mg/dL per 0.1 unit reduction of pH values and 3.6 mg/dL per 1 mmol/L reduction of BE levels) and an increase in red blood cells transfusion (2.16 units of RBC per 0.1 unit reduction of pH and 0.38 units of RBC per 1 mmol/L reduction of BE levels). Among multiple factors potentially associated with adverse outcomes, decreasing pH levels were independently associated with the length of hospitalization but not with in-hospital mortality. Metabolic acidosis is independently associated with decreased fibrinogen levels and increased intraoperative transfusion requirement during OLT. Awareness of that association may improve treatment strategies to reduce intraoperative bleeding risk in OLT.