We conducted a prospective, observational study to determine the incidence of feeding intolerance (FI) within 7 d 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 7 d 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 and epilepsy) and prolonged mechanical ventilation (> 48 h)), patients were divided into poor prognosis and good prognosis groups. The mean age of the 237 CPB patients, including 139 men and ninety-eight women, was 53·80 (sd 12·25) years. The incidence of FI was 64·14 %. Multivariate logistic regression analysis showed factors independently associated with poor prognosis after CPB included FI (OR 2·138; 95 % CI 1·058, 4·320), age (OR 1·033; 95 % CI 1·004, 1·063), New York Heart Association (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 7 d of EN after CPB was high, which was associated with a poor prognosis.