Purpose: Intravascular optical coherence tomography (IV-OCT) is a high-resolution imaging method used to visualize the microstructure of arterial walls in vivo. IV-OCT enables the clinician to clearly observe and accurately measure stent apposition and neointimal coverage of coronary stents, which are associated with side effects such as in-stent thrombosis. In this study, the authors present an algorithm for quantifying stent apposition and neointimal coverage by automatically detecting lumen contours and stent struts in IV-OCT images. Methods: The algorithm utilizes OCT intensity images and their first and second gradient images along the axial direction to detect lumen contours and stent strut candidates. These stent strut candidates are classified into true and false stent struts based on their features, using an artificial neural network with one hidden layer and ten nodes. After segmentation, either the protrusion distance (PD) or neointimal thickness (NT) for each strut is measured automatically. In randomly selected image sets covering a large variety of clinical scenarios, the results of the algorithm were compared to those of manual segmentation by IV-OCT readers. Results: Stent strut detection showed a 96.5% positive predictive value and a 92.9% true positive rate. In addition, case-by-case validation also showed comparable accuracy for most cases. High correlation coefficients (R > 0.99) were observed for PD and NT between the algorithmic and the manual results, showing little bias (0.20 and 0.46 mu m, respectively) and a narrow range of limits of agreement (36 and 54 mu m, respectively). In addition, the algorithm worked well in various clinical scenarios and even in cases with a low level of stent malapposition and neointimal coverage. Conclusions: The presented automatic algorithm enables robust and fast detection of lumen contours and stent struts and provides quantitative measurements of PD and NT. In addition, the algorithm was validated using various clinical cases to demonstrate its reliability. Therefore, this technique can be effectively utilized for clinical trials on stent-related side effects, including instent thrombosis and in-stent restenosis. (C) 2016 American Association of Physicists in Medicine.