Non-steroidal anti-inflammatory drugs (NS-AIDs) are among the most widely prescribed drugs. In this study, we compared the efficacies of four NSAIDs to inhibit lung tumorigenesis in A/J mice. The tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), was given in drinking water between week 0 and week +7. Groups of 25 mice were fed sulindac (123 mg/kg diet), ibuprofen (263 mg/kg), piroxicam (25 mg/kg) or naproxen (230 mg/kg) in AIN-76A diet from week -2 to the end of the bioassay (week +23). Sulindac was the most effective inhibitor and reduced lung tumor multiplicity by 51%. Ibuprofen and piroxicam reduced lung multiplicity by 38% and 30%, respectively. Naproxen demonstrated no inhibitory capacity. Forestomach tumor multiplicity and incidence were both reduced by sulindac and ibuprofen. Sulindac administered from week -2 to week +7 was less effective (28% inhibition) than when given throughout the bioassay. Sulindac induced more intestinal adhesions than any other NSAID and was directly related to the cumulative dose of sulindac. These results show that chemoprevention of lung tumorigenesis by NSAIDs is not limited to sulindac although it is the most effective.