Background and Aims: The information regarding the incidence of acute kidney injury (AKI) in medical Intensive Care Units (ICUs) in South India is limited. The aim of the study was to find the incidence, prognostic factors, and outcome of patients with AKI. We also assessed whether only urine output criteria of risk, injury, failure, loss, end (RIFLE) classification can be used to look at the outcome of AKI. Patients and Methods: This was a prospective, cross-sectional study of 6 months duration in a 28 bedded medical ICU of a tertiary center. AKI was defined as an absolute creatinine value of>1.6 mg/dl or a 25% increase from baseline creatinine values. Results: The incidence of AKI was 16.1%, and mortality was 7.8% in our study population. Among patients with AKI 87 (75.7%) patients had sepsis. 71.3% patients had metabolic acidosis on admission, and 47.8% patients were in shock. 57.4% of patient's required mechanical ventilation (MV). 39.1% of AKI patients required renal replacement therapy (RRT). Requirement of RRT was significantly affected by increasing age, Acute Physiology and Chronic Health Evaluation II and sequential organ failure assessment scores on admission, serum creatinine, and use of vasopressors. 49.5% of patients with AKI died within 28 days. Increasing age, MV, hemodialysis (HD), hypertension, chronic kidney disease, and requirement of noradrenaline support were associated with increasing 28 days mortality. The maximum RIFLE score with urine output criteria showed association to the requirement of HD in univariate analysis but did not show relation to mortality. Conclusion: The incidence of AKI was 16.1% in critically ill patients. In patients with AKI, 39.1% patients required HD and 28 days mortality was 49.5%. The study also showed good univariate association of urine output criteria of RIFLE classification to the requirement of HD in AKI patients.