OBJECTIVE: The purposes of this study were to characterize the pattern of Specific Cyclo-oxygenase Inhibitors (C2I) use, and to determine cost impact of C2I use among patients who were at low risk for gastrointestinal adverse events compared with Non-steroidal anti-inflammatory drug (NSAIDs) use at Lerdsin Hospital, the Special Institution for Orthopedics of Ministry of Public Health, Bangkok, Thailand. METHODS: Retrospective data from medical charts of patient receiving C2I or NSAIDs when visiting orthopedic outpatient clinic were reviewed. Data were collected during November and December 2002. Sample size of patients receiving C2I and NSAIDs was calculated based on the proportion of high and low risk of gastrointestinal adverse events from our pilot study. The National Institute for Clinical Excellence of the United Kingdom Guidances for C2I use was employed to determine whether the patients receiving C2I were at high risk. Drug cost was calculated based on drug acquisition cost. RESULTS: Of the 1113 patient medical records, which were reviewed, 40.1 % of 519 patients receiving C2I and 19% of 594 patients receiving NSAIDs were considered to be at high risk. Of the patients receiving C2I, 112 (21.6%) received C2I alone and 159 (30.6%) received gastro-protective agents in addition to C2I. Prescribing C2I among low risk resulting in excessive expenditure were 2.4 million Baht/year compared with NSAIDs in actual practice. Compared with each of the three highest volumes of NSAIDs used in the hospital (diclofenac, Voltaren ®, and ibuprofen 400 mg), excessive expenditures were 3.4, 1.7, and 3.2 million Baht/year, respectively. CONCLUSION: Cost impact of C2I use among patients who were at low risk for gastrointestinal adverse events compared with NSAIDs at Lerdsin Hospital was 2.4 million Baht/year. Because of the high cost impact of C2I use, it is necessary to employ clinical practice guideline for prescribing restriction in low risk patients.