OBJECTIVES: To examine the drug switching events among non-steroidal anti-inflammatory drugs (NSAIDs) users and co-medication with gastro-protective drugs (GPDs) as an early determinant of dissatisfaction from gastrointestinal (GI) adverse events. METHODS: The Taiwan Longitudinal Health Insurance Database 2000 during 1997 to 2008 was used to identify patients with newly diagnosis of RA (ICD-9-CM: 714.0-714.3) or OA (715.0-715.9) in 1998-2007 to allow for one or more follow-up year. For each patient, the intervals were identified by any gaps of 30 or more days between drug dispensing coverage. Intervals were classified into 3 categories: traditional NSAID (tNSIAD), preferential (pC2SI: meloxicam, etodolac, nabumetone and nimesulide) or specific COX-2 selective inhibitor (COXIB: celecoxib, rofecoxib and etoricoxib). For each patient-interval, the event of switching from one of the 3 categories to another was considered as the dissatisfaction with early GI adverse events. Intervals with less than 60 days of NSAID dispensing were excluded. Considering with/without GPDs, these intervals were divided into 7 medication groups: tNSAID alone, COXIB alone, or pC2SI alone, tNSAID with histamine-2 antagonist (H2RA), proton pump inhibitor (PPI), COXIB, or pC2SI. The Cox regressions with covariates including age, gender, number of prior GI hospitalization, co-medication, comorbidity were used to estimate the hazard ratios (HRs) of drug switching among medication groups. RESULTS: There were 271,683 intervals identified from 97,834 patients. Given no prior GI history, patients in tNSIAD+H2RA and tNSIAD+PPI were significantly less likely to switch (HR=0.63, 95%CI=0.61-0.65); HR=0.82, 95%CI=0.72-0.93) than the tNSAID only. The HRs for drug switching in COXIB, tNSIAD+ COXIB, pC2SI and tNSIAD+pC2SI, however, were 8.04, 6.64, 10.353 and 9.93 (all p value<0.0001), respectively. CONCLUSIONS: Combination of H2RA or PPI was shown less likely to switch than tNSAID alone. These results suggest that H2RA or PPI could be an acceptable augmentation in clinical practice for reducing potential GI adverse events.