inhibitor (PPI) esomeprazole in the third copayment tier on the TRICARE formulary on July 17, 2005. The change to nonpreferred formulary status for esomeprazole included a $13 copayment increase (from $9.00 to $22.00) for either a 30-day supply purchased from a community pharmacy or a 90-day supply purchased from the mail-order pharmacy and a $0 copayment if obtained from a military pharmacy but with a prior authorization (PA) requirement. The change to nonpreferred formulary status was designed to encourage the use of PPIs other than esomeprazole and to increase the use of the mail-order pharmacy for esomeprazole purchases. To quantify changes in (a) the TRICARE beneficiary utilization of esomeprazole relative to other PPIs and (b) the pharmacy settings used for filling esomeprazole prescriptions following implementation of a copayment increase and nonpreferred formulary status for esomeprazole. A census of outpatient pharmacy fill records for prescription acid-reducing medications (PPIs, histamine-2 blockers, misoprostol, and sucralfate) obtained by beneficiaries aged 18 years or older from January 1, 2005, through December 31, 2006, was examined. Interrupted time series regression analyses without a control group were used to compare the utilization of esomeprazole relative to other PPIs, as well as the pharmacy setting used to obtain esomeprazole, in the months before and after the formulary change. The rates of continued esomeprazole use, switching to other prescription PPIs (lansoprazole, omeprazole, pantoprazole, and rabeprazole), switching to non-PPI prescription acid-reducing drugs, and discontinued prescription acid-reducing medication use among existing esomeprazole users (i.e., beneficiaries who obtained esomeprazole as the last PPI fill before the formulary change) were calculated overall and for each pharmacy setting used prior to the formulary change. Over the 24-month study period from January 1, 2005, through December 31, 2006, the total numbers of PPI fills and PPI users increased by 8.5% and 9.0%, respectively, and the number of esomeprazole users decreased by 4.6%. Of esomeprazole users, the percentages of individuals obtaining esomeprazole from military pharmacies and community pharmacies, respectively, decreased from 1.7% to 1.1% and from 89.7% to 81.7%, while the percentage of individuals obtaining esomeprazole from the mail-order pharmacy increased from 8.8% to 17.6%. Time series analysis yielded a positive, statistically significant growth in esomeprazole fills (beta1=0.114; P=0.012) during the 6-month pre-intervention period (January through June 2005) and a significant reduction in August 2005 (beta2=-5.0%; P<0.001), the month immediately following the formulary change. During the 17-month post-intervention period (August 2005 through December 2006), no statistically significant change in trend for esomeprazole fills (beta3=-0.0265; P=0.534) was observed, although a small increase in the raw number of esomeprazole fills was noted. Among the 117,801 existing esomeprazole users, 86,386 (73.3%) continued using esomeprazole, 17,676 (15.0%) switched to other prescription PPIs, 679 (0.6%) used only non- PPI prescription therapy, and 13,060 (11.1%) discontinued all prescription acid-reducing pharmacotherapy after the formulary change. Significantly higher PPI switching and acid-reducing therapy discontinuation rates were observed among men aged 18-44 years and in TRICARE enrollees relative to women, those over 45 years of age, and those who used other health insurance (P<0.001). Individuals who used military pharmacies, where a PA requirement was implemented, were more likely to change pharmacy settings to obtain esomeprazole (43.8%) than were users of community pharmacies (11.9%) or the mail-order pharmacy (22.8%). Mail-order pharmacy users were less likely to discontinue acid-reducing pharmacotherapy (4.9%) than were community (11.9%) or military (12.9%) pharmacy users (P<0.05). After adjustment for serial correlation, the formulary change was associated with a migration of approximately 5% of all PPI fills and 25% of esomeprazole fills to the preferred PPIs in the first post-intervention month. Over the 17-month post-intervention period, the trend toward increased esomeprazole use was slowed and use of the mail-order pharmacy for esomeprazole fills nearly doubled. Our observed PPI switch rate of 15.0% resembled the rate observed for another insured population that experienced a similar formulary restructuring, but was substantially lower than the rates reported for more sizeable formulary changes. Thus, the present study's copayment differentials for third-tier medications ($19 compared with tier 1 and $13 compared with tier 2 copayments) may be less than the threshold amount required to optimize switching to preferred PPIs.