Background: The impact of target vessel diameter on outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. Aim: To compare the impact of target vessel diameter on CTO PCI outcomes. Methods: We examined the association of vessel diameter with clinical, angiographic characteristics, and procedural outcomes of CTO-PCI in a large multicenter registry. The CTO vessels were classified as small (≤ 2.75 mm), medium (2.76−3.00 mm), and large (> 3.00 mm) diameter. Results: Among 13,423 patients who underwent CTO-PCI at 47 centers between 2012 and 2024, the target CTO vessel was small in 4858 (36%), medium in 5393 (40%), and large in 3172 (24%). Compared with patients who had medium and large CTO target vessels, those who had small vessels were older and had a higher prevalence of diabetes, hypertension, dyslipidemia, and peripheral arterial disease. Large target vessel diameter CTOs had more complex angiographic characteristics such as higher J-CTO scores, longer lesion length, and more complex angiographic characteristics. Compared with CTO PCI of small and large vessel patients, medium vessel patients had higher technical (p = 0.008) and procedural (p = 0.010) success. The incidence of perforation was higher in large-diameter vessels. In multivariable logistic regression using restricted cubic spline analysis, a vessel diameter of 2.75−3.00 mm was associated with higher technical (OR 2.05 95% CI 1.12−3.76; p < 0.001) and procedural (OR 2.48 95% CI 1.49−4.13; p < 0.001) success compared with a vessel diameter of less than 2.75 or greater than 3.00 mm. Conclusions: Large and small CTO target vessels were associated with lower technical and procedural success compared with medium-sized vessels.