Objective To explore the effects of 24-h fluid accumulation ratio on the prognosis of patients after cardiopulmonary bypass cardiac operation. Methods A single-center prospective observational study was conducted. The adult patients admitted to the Shanxi Bethune Hospital from January 2018 to January 2020 for selective cardiopulmonary bypass cardiac operation were selected. All the patients received therapy with comprehensive strategy after admission to the intensive care unit (ICU)and were divided into two groups: group A with 24-h fluid accumulation equal to or more than 10% and group B with less than 10%.Sex, age, body mass index (BMI), preoperative acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, preoperative complications, preoperative creatinine levels, intraoperative cardiopulmonary bypass time, deep hypothermic circulatory arrest time, blood loss, fluid intake, incidence of postoperative hypoxemia (oxygenation index ≤150 mmHg), incidence of acute renal injury (AKI), use of mechanical ventilation, duration of ICU stay, and 28-day mortality were compared between the two groups.Risk factors affecting the death of patients after cardiopulmonary bypass cardiac operation were analyzed using logistic regression. Results No significant differences were found between the two groups in gender, age, BMI, preoperative APACHE Ⅱ score,preoperative acute physiology preoperative creatinine, intraoperative cardiopulmonary bypass time, deep hypothermic circulatory arrest time, blood loss, intraoperative infusion, and crystalcolloid ratio (P>0.05). Compared with group B, incidence of combination with hypoxemia (oxygenation index ≤150 mmHg) and AKI was significantly increased in group A (67.9% vs. 43.3%; 57.1% vs. 36%,P<0.01), but there was no significant difference in usage of continuous renal replacement therapy (CRRT) after ICU admission between the two groups (46.4% vs. 32.3%, P=0.052). Both the duration of mechanical ventilation and the length of stay in the ICU in group A were significantly longer than those in group B [(4.3±2.8) d vs. (3.5±1.7) d, (5.1±3.1) d vs. (4.3±1.9) d, P<0.01].No significant differences were found between both groups in 28-day mortality (P>0.05). After further subgroup analysis found that compared with group B, there were statistically significant differences in the utilization rate of CRRT, duration of mechanical ventilation, and length of ICU stay in group A regardless of whether patients had AKI or not (P<0.05). Compared with group B,there were statistically significant differences in incidence of combination with hypoxemia and 28-day mortality in group A patients with AKI (P<0.05), while there was no statistically significant difference in group A patients without AKI (P>0.05). The results of the univariate logistic regression analysis showed that 24-h fluid accumulation ratio ≥10%, postoperative hypoxemia and AKI,fluid accumulation ratio 24-h after surgery ≥10% combined with AKI were the risk factors of patients after cardiopulmonary bypass cardiac operation (P<0.05). The multivariate logistic regression analysis suggested that postoperative 24-h fluid accumulation ratio≥10% combined with AKI was the independent risk factor of patients after cardiopulmonary bypass cardiac operation (P<0.05). Conclusion 24-h fluid accumulation ratio ≥10% after cardiopulmonary bypass not only increases the risk of hypoxemia and AKI, but also prolongs the duration of mechanical ventilation and ICU hospitalization, and 24-h fluid accumulation ratio ≥10%combined with AKI can increase the risk of death in patients after cardiopulmonary bypass.