We thank Drs Charchaflieh and Zafar1 for their interest in our article2 regarding the effect of caffeine consumption on resident physician’s driving performance variables in a high-fidelity, immersive driving simulator. While Charchaflieh and Zafar1 are correct that we did not measure baseline caffeine consumption in the participants, we would submit that there is limited and conflicting evidence whether regular intake of caffeine alters caffeine pharmacokinetics.3–5 In contrast, there is pronounced variability in CYP1A2 activity influencing caffeine clearance related to sex, race, genetic polymorphisms, liver disease, and exposure to agents that further induce the cytochrome system.6–8 Caffeine is primarily metabolized in the liver by cytochrome P450 enzymes, principally by CYP1A2.6 We did not evaluate for genetic polymorphisms nor construct a caffeine dose-response effect. We did, however, incorporate a self-reported caffeine sensitivity measure from all participants. The dose of caffeine (160 mg) administered in this study is considered a pharmacologic dose, such that the difference between people who are perceived to be more or less resistant to the effects of caffeine is not likely to be relevant. In our study of residents at a single institution, it would have been challenging to control for all of the variables that may have impacted caffeine sensitivity, and for that reason, we used perceived caffeine sensitivity. Most importantly, we used a crossover design where each resident served as their own control, completing both arms of the study (caffeinated versus noncaffeinated energy beverage). To the extent that it is possible, this suggests that any observed effect resulted from the caffeine. Drs Charchaflieh and Zafar1 are correct that we did not use the word “simulated” in the title. We feel very strongly that this is not misleading as the aim of our study, stated in both the Introduction and the Conclusion, was to evaluate the impact of a caffeinated energy beverage on driving performance in a high-fidelity driving simulator. The Methods section clearly indicates that the study was performed in the simulator, and the Results section refers directly to improved driving performance variables in the driving simulator. Finally, we note that the words “simulated,” “simulation,” and “simulator” occur 37 times in the article, including 4 times in the Abstract alone! We do not agree with Charchaflieh and Zafar’s1 statement at the end of their letter that suggests that our title or reporting of results within sections of the article are at all misleading or “considered less than accurate.” Julie L. Huffmyer, MDDepartment of AnesthesiologyUniversity of Virginia HealthCharlottesville, Virginia[email protected]Edward C. Nemergut, MDDepartments of Anesthesiology and NeurosurgeryUniversity of Virginia HealthCharlottesville, Virginia