We conducted a prospective, observational study to determine the incidence of feeding intolerance (FI) within seven days of initiating enteral nutrition (EN) in patients undergoing cardiopulmonary bypass (CPB), and to evaluate the association between FI and a poor prognosis. Patients who underwent CPB surgery at Fujian Medical University Union Hospital between March 2020 and June 2020 were enrolled. According to the presence or absence of FI within seven days after EN, patients were divided into FI and non-FI groups. According to the occurrence of a poor prognosis (death, gastrointestinal haemorrhage, acute kidney injury, liver insufficiency, neurological events [cerebral infarction, cerebral haemorrhage, epilepsy], and prolonged mechanical ventilation [>48 hours]), patients were divided into poor prognosis and good prognosis groups. The mean (standard deviation) age of the 237 CPB patients, including 139 men and 98 women, was 53.80 ± 12.25 years. The incidence of FI was 64.14%. There were 152 cases in the FI group and 85 cases in the non-FI group. Multivariate logistic regression analysis showed factors independently associated with poor prognosis after CPB included FI (odds ratio [OR], 2.138; 95% confidence interval [CI], 1.058–4.320), age (OR, 1.033; 95% CI, 1.004–1.063), NYHA class III - IV cardiac function (OR, 2.410; 95% CI, 1.079–5.383), macrovascular surgery (OR, 5.434; 95% CI, 1.704–17.333), and initial sequential organ failure assessment score (OR, 1.243; 95% CI, 1.010–1.530). Thus, the incidence of FI within seven days of EN after CPB was high, which was associated with a poor prognosis.