BACKGROUND: Clinical guidelines recommend that patients at high risk for upper gastrointestinal (UGI) complications using chronic non-selective non-steroidals (ns-NSAIDs) or COX-2 inhibitors (COXIBs) for arthritis pain management should concomitantly take gastroprotective (GPA) therapy; however, GPA use and adherence are often low and associated with an increase in UGI events. OBJECTIVES: To evaluate the budget impact of adherence to concomitant GPA therapy among patients using ns-NSAIDs or COXIBs at high risk for NSAID-induced UGI events.  METHODS: The impact of GPA adherence was assessed using a budget impact model with a one-year time horizon.  UGI risk is a function of patient (age, previous ulcer history, concomitant low dose aspirin use) and treatment (ns-NSAID or COXIB, concomitant GPA use and adherence) characteristics.  Mean GPA adherence rate of 51% was derived from the MarketScan Research Databases, using a sample of patients ≥ 50 y/o with at least 2 prescriptions for ns-NSAIDs or COXIBs from 2001 through 2007 (N=738,248).  Treatment-specific UGI event rates and costs were taken from the literature for dyspepsia, symptomatic ulcers and UGI bleeding. Sensitivity analysis was performed around the model inputs.  RESULTS: In the model basecase, NSAID-induced UGI events are responsible for $8,285,363 in direct medical costs annually in a hypothetical health plan with 100,000 members, where 21.6% of patients are on chronic ns-NSAID or COXIB therapy for arthritis and 85.6% of these patients are at increased risk of a UGI event due to age, previous ulcer history, or both.  Increasing GPA adherence to 75% decreases NSAID-induced UGI event costs by $486,312, or $0.41 per-member-per-month (PMPM) in a 100,000-member health plan; reducing GPA adherence to 25% increases these costs by $656,248 ($0.55 PMPM).  CONCLUSIONS: GPA adherence has a strong impact on the cost associated with NSAID-induced UGI events.  This finding was consistent throughout sensitivity analyses varying risk factors and costs of UGI events.