Aims: The aim of the present study was to explore the level of risk associated with community use of non-steroidal anti-inflammatory drugs (NSAIDs). Methods: We carried out a matched case-control study of the relationship between recent use of NSAIDs and the presence of functional renal impairment present at the time of hospitalisation with a range of clinical problems. Cases (n = 110) were consecutive patients admitted acutely to hospital who had serum creatinine levels greater than or equal to 0.15 mmol l-1, which improved by 20% or more within the next 14 days, or prior to discharge from hospital. Controls (n = 189) were subjects of the same sex and age (to within 5 years) as the cases, who were admitted to the same hospital, who had normal serum creatinine levels (<0.12 mmol l-1) throughout their hospital stay. Information on a number of study factors, including recent use of aspirin and other NSAIDs, was obtained by structured interview. Results: Overall, there was a weak association between consumption of NSAIDs (including non-prophylactic aspirin) and the development of functional renal impairment-adjusted odds ratios (OR) with use of NSAIDs in the previous week or in the previous month: OR 1.5 (95% CI 0.80, 2.9) and 1.8 (95% CI 0.97, 3.4) respectively. In subjects with a previous history of renal disease the adjusted OR was 6.6 (0.75, 57.8) and in those with a history of gout or hyperuricaemia the OR was 7.2 (1.3, 40.2). There was a weak positive relationship between the dose of drug consumed in the previous week and the odds of functional renal impairment. The relationship between risk and published figures for drug half-lives (t( 1/4 )) was stronger. The odds ratio increased from 1.2 (95% CI 0.61, 2.4) with a t( 1/4 ) ≤ 4 h, to 4.8 (1.5, 15.8) with a t( 1/4 ) of ≤ 12h (P = 0.012, test for trend). This relationship remained statistically significant after adjustment for a number of clinical variables and the dose of drug ingested. Conclusions: NSAIDs are an important cause of functional renal impairment in subjects with renal disease or a history of gout or hyperuricemia. The half-life of the drug is more important than the ingested dose in determining the risk of this outcome. Long half-life drugs should be avoided in individuals who are at risk of developing renal impairment.