Background: Gallic acid (3,4,5-trihydroxybenzoic acid) is a natural polyphenol and strong natural antioxidant found abundantly in red wine and green tea. The aim of this study was to examine the anti-inflammatory effect of a novel gallic acid-eluting stent in a porcine coronary restenosis model. Methods: Fifteen pigs were randomized into three groups; in which a total of 30 coronary arteries (10 in each group) were implanted with gallic acid-eluting stents (GESs, n = 10), gallic acid and sirolimus-eluting stents (GSESs, n = 10), or sirolimus-eluting stents (SESs, n = 10). Histopathologic analysis was performed 28 days after stenting. Results: There were no significant differences in injury score and fibrin score among the groups, however there were significant differences in the internal elastic lamina (4.0  0.83mm2 in GES vs. 3.0  0.53mm2 in GSES vs. 4.6  1.43 mm2 in SES, p < 0.0001), lumen area (2.3  0.49 mm2 in GES vs. 1.9  0.67 mm2 in GSES vs. 2.9  0.56 mm2 in SES, p < 0.0001), neointimal area (1.7  0.63 mm2 in GES vs. 1.1  0.28 mm2 in GSES vs. 1.7  1.17 mm2 in SES, p < 0.05), and percent area of stenosis (42.4%  9.22% in GES vs. 38.2%  12.77% in GSES vs. 33.9%  15.64% in SES, p < 0.05). The inflammation score was significantly lower in the GES and GSES groups compared to that in the SES group [1.0 (range: 1.0 to 2.0) in GES vs. 1.0 (range: 1.0 to 1.0) in GSES vs. 1.5 (range: 1.0 to 3.0) in SES, p < 0.05]. Conclusions: The GES group had a greater percent area of stenosis than the SES group. Although gallic acid in the GES and GSES groups did not show a synergistic effect in suppressing neointimal hyperplasia, it resulted in greater inhibition of the inflammatory reaction in the porcine coronary restenosis model than in the SES group.