Objective: To evaluate the effect of different connection modes of ECMO and CRRT on patients with acute kidney injury (AKI). Methods: Twenty-one patients received ECMO with AKI who were admitted to our center from December 2018 to February 2021 were selected and were all treated with both ECMO and CRRT. They were divided into A connection mode (pre-membrane–pre-pump connection) and B connection mode (post-membrane–post-pump connection). We compared clinical indicators and outcomes between two connection modes. Results: There were 8 cases (38.91%) in A connection mode and 13 cases (61.09%) in B connection mode, with median durations of ECMO assistance of 5 days and 7 days, respectively; median flow rates of ECMO of 3.0 L/min and 2.5 L/min, respectively; and CRRT flow rates of 200 mL/min and 180 mL/min, respectively. CRRT filter lifetime was over 48h in both two connection modes. Except for NT-pro BNP, no significant differences in clinical indicators were observed between the two groups before or after the treatment (P > 0.05). Conclusion: Both two connection modes could achieve the therapeutical purpose and need not higher level of anticoagulation who are simultaneously treated with ECMO and CRRT. Two modes had no impact on treatment effect and clinical indicators in patients. It had no effect on length of ICU stay and prognostic.