Background: For the coronavirus disease 2019 (COVID 19), critically ill patients had a high mortality rate. We aimed to assess the association between prolonged intermittent renal replacement therapy (PIRRT) and mortality in patients with COVID 19 undergoing invasive mechanical ventilation. Methods: In this retrospective cohort study, we included all patients with COVID 19 undergoing invasive mechanical ventilation from February 12nd to March 2nd, 2020. All patients were followed until death or March 28th, and all survivors were followed for at least 30 days. Results: For 36 hospitalized COVID 19 patients with invasive mechanical ventilation, the mean age was 69.4 (10.8) years, and 30 patients (83.3%) were men. Twenty two (61.1%) patients received PIRRT (PIRRT group) and 14 cases (38.9%) were managed with conventional strategy (non PIRRT group). There were no differences in age, sex, comorbidities, complications, treatments and most of the laboratory findings. During median follow up period of 9.5 (interquartile range 4.3， 33.5) days, 13 of 22 (59.1%) patients in the PIRRT group and 11 of 14 (78.6%) patients in the non-PIRRT group died. Kaplan Meier analysis demonstrated prolonged survival in patients in the PIRRT group compared with that in the non PIRRT group (P = 0.042). The association between PIRRT and a reduced risk of mortality remained significant in three different models, with adjusted hazard ratios varying from 0.332 to 0.398. Higher levels of IL2 receptor, TNFa, procalcitonin, prothrombin time, and NT proBNP were significantly associated with an increased risk of mortality in patients with PIRRT. Conclusion: PIRRT may be beneficial for the treatment of COVID 19 patients with invasive mechanical ventilation. Further prospective multicenter studies with larger sample sizes are required.