OBJECTIVE The inflammatory response elicited by robotically enhanced coronary artery bypass grafting (r-CABG) has not been well described. When r-CABG is performed as part of hybrid coronary revascularization, the inflammatory milieu and the timing of percutaneous coronary intervention may affect the stent patency negatively in the short and long term. The goal of this study was to describe the extent and time course of cytokine release after r-CABG compared with conventional CABG (c-CABG) and to elucidate the optimal timing for r-CABG in the setting of hybrid coronary revascularization for a future study. DESIGN Prospective, observational study. SETTING Tertiary-care center in a university hospital. PARTICIPANTS The study comprised patients scheduled to undergo r-CABG or c-CABG from October 2012 to November 2014. INTERVENTIONS Cytokine levels of interleukin (IL)-6, IL-8, IL-10; tumor necrosis factor-α; and C-reactive protein (CRP) were measured at the following time points: preprocedure; at the end of the procedure; and at 4, 8, 12, 24, and 48 hours after the procedure. MEASUREMENTS AND MAIN RESULTS Twenty-eight patients undergoing r-CABG and 10 patients undergoing c-CABG were enrolled. The levels of cytokines after r-CABG and c-CABG were compared using the mixed-effect linear regression model for longitudinal data. Cytokine release in the r-CABG group was comparatively less for IL-6, IL-10, tumor necrosis factor, and CRP levels. They all trended toward the baseline by the 48th hour in both groups, except CRP levels, which reached their peak at 48 hours in both groups. CONCLUSIONS The inflammatory response to r-CABG was blunted compared with that of c-CABG. The high CRP levels on the second postoperative day after r-CABG were a cause for concern in regard to percutaneous coronary intervention performed at that time period, but additional studies are necessary.