The aim of this study was to identify predisposing factors for coronary in-stent restenosis (ISR) and assess its detection by 320-row computed tomography angiography (CTA) using invasive coronary angiography (ICA) as a gold standard. A total of 189 patients (aged 35–79, mean age 56.6, 169 males) with 318 stents underwent ICA within 4 days after CTA. ISR was found in 19 (10.0 %) patients and 25 (7.9 %) stents. At the patient level, the presence of ISR was significantly related to the number of deployed stents (P = 0.026) and body mass index (P = 0.030). At the stent level, stents with diameter <3 mm were more likely to have ISR than those with diameter ≥3 mm (53.8 % vs. 28.9 %, P = 0.016). Bare metal stents were significantly more likely to have ISR than drug-eluting stents (15.2 % vs. 6 %, P = 0.022). ISR was not significantly related to stent length (P = 0.097) and stent placement in coronary arteries at the vessel level (P = 0.059). False-positive or false-negative results of CTA were not related to stent location, diameter, length, and strut thickness (P > 0.05). At the patient level, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CTA for detecting ISR were 90, 96, 74, 99, and 96 %, respectively. At the stent level, the corresponding figures were 92, 96, 67, 99, and 96 %. The high negative predictive value of 99 % suggests that 320-row CTA is helpful for excluding ISR.