Renal prostaglandin inhibition by nonsteroidal antiinflammatory drugs(NSAIDs)may decrease renal function, especially under conditions of low effective circulating volume. To evaluate the risk important deterioration of renal function due to this effect, the authors preformed a nested case-control study using Tennessee Medicaid enrollees aged ≥65 years in 1987–1991. Cases were patients who had been hospitalized with community acquired acute renal failure; they were selected on the timing, duration, and close of prescription NSAIDs used demographic factors, and comorbidity was gathered from computerized Mdeical-Medicare data files of the 1,799 patients with acute renal failure (4.51 hospitalizations per 1, 000 preson-years), 18.1% were current users of prescrition NSAIDs as compared with 11.3% of 9, 899 randomly selected population controls, After control for demogarphic factors and commorbidity, use of NSAIDs increased the risk of acute renal failure 58%(adjusted odds ratio = 1.58; 95% confidence interval (CI): 1.34, 1.66). For ibuproten, which accounted for 35% of NSAID use, odds ratio associated with dosages of ≤ 1,200 mg/day, > 1,200—2,400 mg/day, were 0.94(95% CI: 0.58, 1.51), 1.89(95% CI: 1.34, 2.67), and 2.32(95% CI: 1.45, 3.71), respectively (test for linear trend: p = 0.009). Prescription NSAID use resulted in an estimated 25 excess hospitalizations associated with renal failure per 10,000 years of use. Thus, NSAIDs represent a relatively uncommon but avoidable cause of acute renal failure in trail elderly persons. Am J Epidemiol 2000;151:488–96.