Pigs are one of the important experimental animals for cardiovascular research. Few porcine coronary atherosclerosis models have been developed; however, the induction of which requires longer than 6 months. We developed a porcine coronary artery atherosclerosis model using nicotine injection with a balloon overdilation. A coronary balloon was placed in the porcine coronary artery and was over dilated to induce a mechanical injury. Nicotine was administrated via intramuscular injection every day and changes in the coronary artery were observed after 4 weeks. Coronary angiography revealed nicotine injection with a balloon overdilation groups showed narrowing of the coronary artery at the injury site. Combination of balloon and nicotine significantly increased the intimal hyperplasia on optical coherence tomography analysis. Proliferated tunica media was noted in the nicotine injection with balloon overdilation groups. Quantitative analysis showed increased smooth muscle actin alpha (SMA), cluster of differentiation 68 (CD68), and Krüppel-like factor 4 (KLF4) in the nicotine injection with balloon overdilation groups. The immunohistochemistry results showed CD68-positive cells displayed SMA- and KLF4-positive reactivity in the border zone of intimal hyperplasia. Our results show that nicotine injection with balloon overdilation can induce an atherosclerosis lesion within one month, which mimics the human atherosclerosis.