Background: Diuretic use in acute kidney injury (AKI) is debatable. Contrasting outcomes have been reported regarding its efficacy in AKI. Sequential nephron blockade (SNB) has never been studied in a diverse ICU population admitted with AKI.Methods: Consecutive patients admitted to medical ICU with oliguric AKI over 1-year period were recruited. SNB as a diuretic strategy was administered. Responders (R) and non-responders (NR) were compared. Demographic data, clinical profile, treatment and outcomes were compared between the groups using t-test and Chi-square test as appropriate. Predictors of mortality were explored using bivariate and multivariate logistic regression analysis and expressed as Odds ratio (OR) with 95% confidence interval (CI). Results: Of the 331 ICU patients admitted with AKI, 312 patients received SNB. The mean (SD) age was 64.14±14·79 years with male preponderance (196:116). Admission SOFA score was significantly (p<0·001) higher (9.6±3.8) in non-responders than responders (6·3±3.6). Overall, 80.13% patients were responders and 19.6% patients received RRT. Significant difference (p<0·001) for diuretic response and dialysis were seen with pre-existing diabetes, higher KDIGO stage and SOFA score (>9) at ICU admission, sepsis, shock, mechanical ventilation, positive fluid balance, lengthy ICU stay and mortality. On multivariate logistic regression analysis, SOFA score >9(OR 4.50; 95%CI 2.30-8.80), negative diuretic response (OR 0.45; 95%CI 0.34-0.59), RRT need (OR 1.78; 95%CI 1.25-2.19) and a higher positive fluid balance (OR 2.82; 95%CI 1.76-3.89) were independently associated with death. Conclusions: SNB in oliguric AKI patients resulted in lesser need for dialysis and better outcomes. A negative response, need for dialysis and a higher positive fluid balance were independently associated with mortality.