Noninvasive assessment of coronary in-stent restenosis (ISR) is clinically useful but 4- and 16-slice multidetector computed tomography is limited due to stent strut artifacts. We evaluated the feasibility and accuracy of 64-slice multidetector computed tomography in the diagnosis of ISR to validate its accuracy in ISR quantification and identify factors that may affect stent patency evaluability. One hundred patients with previously implanted coronary stents (n = 179) underwent 64-slice multidetector computed tomography followed by invasive coronary angiography. After multidetector computed tomography, each stent was classified as "evaluable" or "unevaluable." Obstructive ISR was visually and quantitatively determined in evaluable stents. Correlations between quantitative multidetector computed tomography and quantitative coronary angiography were estimated. In a subgroup, multidetector computed tomographic and intravascular ultrasound measurements were correlated. Feasibility of stent visualization was 95%. Thirty-four of 39 ISRs (87%) were correctly detected and localized by multidetector computed tomography. ISR was correctly ruled out for 77% (128 of 131) of remaining stented lesions. Sensitivity, specificity, and positive and negative predictive values of multidetector computed tomography for ISR identification were 87%, 98%, 92%, and 96%, respectively. There was good correlation between percent stenosis evaluated by multidetector computed tomography versus quantitative coronary angiography and intravascular ultrasound (r = 0.794, p <0.001, and r = 0.943, p <0.0001, respectively) and good reproducibility of multidetector computed tomographic measurements (interobserver coefficient k 0.81 for diameter and 0.79 for area). Heart rate, complexity of stenting procedure, stent diameter, and strut thickness were factors limiting feasibility and accuracy. In conclusion, 64-slice multidetector computed tomography provides reliable and reproducible noninvasive evaluation of coronary stent patency and quantification of ISR.