To evaluate the association between nonsteroidalantiinflammatory drug (NSAID) use and uppergastrointestinal bleeding (UGIB) and lowergastrointestinal bleeding (LGIB), we performed aprospective case-control study at a large inner-cityhospital over a 28-month period evaluating 461consecutive patients hospitalized for UGIB and 105 withLGIB. During the same period, 1895 in-patients evaluatedby our gastroenterology consultative service served ascontrols. At the time of initial evaluation, allpatients were asked about the use of any prescription orover-the-counter NSAID product within one week of admission. Endoscopic examination was performedin most patients with bleeding. NSAID use was almostequivalent in patients with UGIB and LGIB (60%) andsignificantly greater than controls [34%; P < 0.001;="" odds="" ratio="" (or)="" 3.0;="" 95%="" ci,="" 2.4-3.6].="" the="" age,race,="" and="" gender="" adjusted="" risk="" for="" lgib="" associated="" withnsaid="" use="" was="" significant="" [adjusted="" or="" (aor)="" 2.6;="" 95%="" ci1.7-3.9],="" although="" less="" than="" ugib="" (aor="" 3.2;="" p="0.34)." the="" risk="" associated="" withdiverticular="" bleeding="" (n="53," aor="" 3.4;="" 95%="" ci="" 1.9-6.2)was="" higher="" than="" duodenal="" ulcer="" bleeding="" although="" notsignificantly="" (n="97," aor="" 3.0).="" we="" conclude="" that="" nsaiduse="" is="" strongly="" associated="" with="" lgib="" and="" from="" lesionsnot="" considered="" associated="" with="" mucosal="" ulceration="" suchas="">