Abstract Background Recent data suggest the regime of fluid therapy intraoperatively in patients undergoing major surgeries may interfere in patient outcomes. The development of postoperative Acute Kidney Injury (AKI) has been associated with both Restrictive Fluid Balance (RFB) and Liberal Fluid Balance (LFB) during non-cardiac surgery. In patients undergoing cardiac surgery, this influence remains unclear. The study objective was to evaluate the relationship between intraoperative RFB vs. LFB and the incidence of Cardiac-Surgery-Associated AKI (CSA-AKI) and major postoperative outcomes in patients undergoing on-pump Coronary Artery Bypass Grafting (CABG). Methods This prospective, multicenter, observational cohort study was set at two high-complexity university hospitals in Brazil. Adult patients who required postoperative intensive care after undergoing elective on-pump CABG were allocated to two groups according to their intraoperative fluid strategy (RFB or LFB) with no intervention. Results The primary endpoint was CSA-AKI. The secondary outcomes were in-hospital mortality, cardiovascular complications, ICU Length of Stay (ICU-LOS), and Hospital LOS (H-LOS). After propensity score matching, 180 patients remained in each group. There was no difference in risk of CSA-AKI between the two groups (RR = 1.15; 95% CI, 0.85-1.56, p= 0.36). The in-hospital mortality, H-LOS and cardiovascular complications were higher in the LFB group. ICU-LOS was not significantly different between the two groups. ROCcurve analysis determined a fluid balance above 2500 mL to accurately predict in-hospital mortality. Conclusion Patients undergoing on-pump CABG with LFB when compared with patients with RFB present similar CSA-AKI rates and ICU-LOS, but higher in-hospital mortality, cardiovascular complications, and H-LOS.