Previous studies have shown that acidic pH and several ingestible substances can cause misleading guaiac tests of gastric aspirates. In this in vitro study, over 100 foods, beverages, and drugs were diluted to concentrations potentially present in the stomachs of outpatients being evaluated for gastrointestinal bleeding. These were mixed with known concentrations of blood and tested with different brands of guaiac cards. Decreased guaiac test sensitivity was associated with activated charcoal, dimethylaminoethanol, red chile, N-acetylcysteine, rifampin, red Jell-O (General Foods Corp, White Plains, NY), orange juice, Pepto-Bismol (Norwich Eaton Pharmaceuticals, Norwich, NY), simethicone, spaghetti sauce, and several red wines. Chlorophyll and methylene blue-containing tablets produced false-positive results, but other blue and blue-green colored tablets did not, except at high concentrations. Previously described false-negative results with vitamin C, bile, and certain antacids were confirmed, as were false-positive results with iodide, bromide, cupric sulfate, iron salts, and hypochlorite. Physicians should exercise caution when interpreting guaiac card tests of gastric aspirates, especially in the outpatient setting.