Background: Determining the timing of renal replacement therapy (RRT) in patients with acute kidney injury (AKI) and heart failure (HF) can optimize the clinical management strategy. We compared the impact of "early" and "delayed" timing of RRT on the prognosis of patients with AKI and HF.Methods: Clinical data from September 2012 to September 2022 were retrospectively analyzed. Patients with AKI complicated by HF and undergoing RRT in the intensive care unit (ICU) were enrolled. Patients with stage 3 AKI and fluid overload present (FOP) or who met the emergency indications for RRT were assigned to the delayed RRT group. Patients with stage 1 AKI or stage 2 AKI and without urgent indications for RRT and patients with stage 3 AKI without FOP and without urgent indications for RRT were enrolled in the Early RRT group. At 90-day follow-up after initiation of RRT, the mortality was compared between the two groups. Logistic regression analysis was performed to adjust for confounding factors affecting 90-day mortality.Results: A total of 151 patients were enrolled, including 77 in the early RRT group and 74 in the delayed RRT group. For baseline characteristics, patients in the early RRT group had significantly lower acute physiology and chronic health evaluation-II (APACHE-II) score, sequential organ failure assessment (SOFA), serum creatinine (Scr) values and blood urea nitrogen (BUN) values on the day of ICU admission than those in the delayed RRT group (both P values <0.05), there were no significant differences in other baseline characteristics. The number of RRT-free days in the ICU was significantly longer in the early RRT group than in the delayed RRT group [1.69 (0.35-10.87) vs. 0.88 (0.20-4.55) days; P=0.046]. However, clinical outcomes (except for the number of RRT-free days) and complications showed no significant differences between these 2 groups (all P values >0.05). Multivariate binary logistic regression analysis showed early initiation of RRT was not an independent risk factor for increased 90-day mortality [odds ratio (OR): 0.671; 95% confidence interval (CI): 0.314-1.434; P=0.303].Conclusions: Early initiation of RRT is not recommended to reduce mortality in AKI patients with HF.