Objective To observe the levels of angiopoietin (Ang) and Tie2 in the peripheral blood of patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and analyze their relationship with patient prognosis. Methods Thirty one patients scheduled for cardiac surgery with CPB from January 2017 to December 2017 were enrolled. Their peripheral blood samples were collected before surgery (T1), 6 h after surgery (T2), Day 1 after surgery (T3), Day 3 after surgery (T4), and Day 5 after surgery (T5) to measure and compare the level of lactic acid (Lac) and blood cell counts. The enzyme‑linked immunosorbent assay (ELISA) was adopted to determine and compare the levels of plasma Ang‑1, Ang‑2 and soluble Tie2 (sTie2). The relationship between the levels of Ang and Tie2, and the duration of CPB and the length of postoperative stay in the intensive care unit (ICU) for the patients were analyzed. Results Compared with those at T1, the number of white blood cells (WBCs) and neutrophils remarkably increased from T2 to T5, the level of Lac obviously increased at T2, at T3 and T4, the concentration of Ang‑1 obviously decreased, and the concentration of Ang‑2 obviously increased, and the ratio of Ang‑1/Ang‑2 and sTie2 level remarkably declined from T2 to T4 (P<0.05). Compared with those at T2, the level of Lac obviously decreased from T3 to T5, at T3 and T4, the concentration of Ang‑1 and the ratio of Ang‑1/Ang‑2 remarkably declined, and the concentration of Ang‑2 obviously increased, and the level of sTie2 remarkably increased at T4 and T5 (P<0.05). Compared with those at T3, the ratio of Ang‑1/Ang‑2 obviously decreased at T4, while the ratio of Ang‑1/Ang‑2 and sTie2 level remarkably increased at T5 (P<0.05). Compared with those at T4, the concentration of Ang‑1 and the ratio of Ang‑1/Ang‑2 remarkably increased at T5 (P<0.05). At T3, the ratio of Ang‑1/Ang‑2 was negatively related with the duration of CPB and the length of ICU stay, with a correlation coefficient of −0.64 and −0.59, respectively (P<0.01), the level of sTie2 was negatively related with the duration of CPB and the length of ICU stay, with a correlation coefficient of −0.93 and −0.69, respectively (P<0.01). Conclusions The levels of plasma Ang and Tie2 dynamically change in the perioperative period of patients undergoing cardiac surgery with CPB, which facilitates patient management after surgery, so as to shorten the length of ICU stay.