ObjectivesCurrent guidelines recommend that enteral nutrition (EN) be implemented as early as possible in patients after cardiopulmonary bypass (CPB), but the optimal time to initiate EN remains controversial. Therefore, the aim of this study was to investigate the effect of timing of EN initiation on poor prognosis in patients after CPB. MethodsThis was a prospective observational study with patients who underwent CPB in a tertiary hospital from September 1, 2021, to January 31, 2022. The patients were divided into three groups according to the timing of EN initiation: <24 h, 24 to 48 h, and >48 h. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals to identify independent risk factors for poor prognosis. ResultsThe study included 579 patients, of whom 255 patients had EN initiated at <24 h (44%), 226 at 24 to 48 h (39%), and at >48 h (17%). With EN <24 h as a reference, multivariate logistic analysis showed that EN 24 to 48 h (OR, 1.854, P = 0.008) and EN >48 h (OR, 7.486, P <0.001) were independent risk factors for poor prognosis after CPB. Age (OR, 1.032, P = 0.001), emergency surgery (OR, 10.051; P <0.001), surgical time (OR, 1.006; P <0.001), and sequential organ failure assessment score (OR, 1.269; P = 0.001) also increased the risk for poor prognosis after CPB. ConclusionsCompared with early EN <24 h, EN 24 to 48 h and EN >48 h increased the risk for poor prognosis in patients after CPB.