In light of recent data indicating that rofecoxib and celecoxib may have differences in clinical and economic outcomes, our analysis may be criticized for grouping both cyclooxygenase-2 inhibitors into the same strategy. For example, a recent case–control study (77) found a higher short-term incidence of upper-GI hemorrhage with rofecoxib versus celecoxib. Moreover, data indicate that dyspepsia rates between rofecoxib and nonselective NSAIDs converge after 6 months (9), whereas celecoxib maintains its dyspepsia risk reduction without convergence (78). In contrast, a multicenter randomized, controlled trial found that rofecoxib provides an efficacy advantage over celecoxib for osteoarthritis of the knee (79). In addition, analysis of a large pharmacy database revealed that patients require a mean of 1.4 celecoxib pills per day (200 mg) versus 1.1 rofecoxib pills per day (25 mg) (80). An analysis of prescribing patterns in the VA system suggests that this disparity may form the economic basis for preferring rofecoxib over celecoxib (81). However, to explicitly bias our model in favor of coxibs, we designed a hypothetical “best-case” coxib that represents the most favorable hybrid between celecoxib and rofecoxib. Four estimates, in particular, exemplify this bias. First, rather than model a higher rate of ulcer complications for rofecoxib than celecoxib, we assumed a favorable 60% risk reduction in ulcer complications for both coxibs compared with naproxen. Second, rather than assume that rofecoxib provided no risk reduction in dyspepsia after 6 months, we assumed that both coxibs provided a 30% reduction over the course of the entire lifetime horizon. Third, rather than assume that the efficacy of celecoxib was inferior to rofecoxib, we assumed that both coxibs were equally effective in providing symptom relief for arthritis pain. Finally, rather than estimate a daily average consumption of 1.4 celecoxib pills and 1.1 rofecoxib pills, we assumed that only 1 pill was required daily for all coxibs. Therefore, where clinical data tend to disfavor rofecoxib (for example, upper-GI hemorrhage and dyspepsia rates), we used celecoxib data, and where clinical data tend to disfavor celecoxib (for example, arthritis efficacy and daily average consumption), we adopted rofecoxib data. Despite modeling this “best-case” hybrid coxib, our analysis suggests that coxibs may not be cost-effective in our base-case cohort.