As more and more studies have shown that venovenous extracorporeal membrane oxygenation (VV-ECMO) improves oxygenation and prognosis of critical patients, VV-ECMO has been frequently used in critical patients for severe acute respiratory distress syndrome (ARDS). Prone positioning (PP) is a postural therapy for ARDS, which permits for better ventilation/perfusion ratio (V/Q) matching, improvement of hypoxemia. Some articles revealed that performing PP during ECMO for refractory respiratory failure is feasible; however, the results obtained were controversial. Therefore, we performed a systematic review to further assess the effects of PP during ECMO for refractory respiratory failure. Six studies with 465 subjects were enrolled. Four articles examined changes of PaO2/FiO2 ratio after PP during VV-ECMO; PaO2/FiO2 ratio improved from 18.5 to 62 mmHg. Our analysis inferred that the PP-ECMO group did not have a significant advantage in survival at discharge (odds risk 1.42, 95% confidence interval 0.92-2.18; p = 0.11) compared with the ECMO group. We found that the PP-ECMO group had a significantly longer duration than the ECMO group (MD 5.37, 95% CI 4.19-6.54, I = 67%, P < .00001). ICU length of stay in the PP-ECMO group was significantly longer than the ECMO group (MD 7.29, 95% CI 4.06-10.52, I = 64%, P < .00001). No unplanned extubation of ECMO was recorded. In conclusion, our review found that performing PP during ECMO for refractory respiratory failure is safe and PP can improve the PaO2/FiO2 ratio, which is in line with the length of PP performed.