We developed machine learning methods to identify fibrolipidic and fibrocalcific A-lines in intravascular optical coherence tomography (IVOCT) images using a comprehensive set of handcrafted features. We incorporated features developed in previous studies (e.g., optical attenuation and A-line peaks). In addition, we included vascular lumen morphology and three-dimensional (3-D) digital edge and texture features. Classification methods were developed using expansive datasets (∼7000  images), consisting of both clinical in-vivo images and an ex-vivo dataset, which was validated using 3-D cryo-imaging/histology. Conditional random field was used to perform 3-D classification noise cleaning of classification results. We tested various multiclass approaches, classifiers, and feature selection schemes and found that a three-class support vector machine with minimal-redundancy-maximal-relevance feature selection gave the best performance. We found that inclusion of our morphological and 3-D features improved overall classification accuracy. On a held-out test set consisting of >1700 images, we obtained an overall accuracy of 81.58%, with the following (sensitivity/specificity) for each class: other (81.43/89.59), fibrolipidic (94.48/87.32), and fibrocalcific (74.82/95.28). The en-face views of classification results showed that automated classification easily captured the preponderance of a disease segment (e.g., a calcified segment had large regions of fibrocalcific classifications). Finally, we demonstrated proof-of-concept for streamlining A-line classification output with existing fibrolipidic and fibrocalcific boundary segmentation methods, to enable fully automated plaque quantification. The results suggest that our classification approach is a viable step toward fully automated IVOCT plaque classification and segmentation for live-time treatment planning and for offline assessment of drug and biologic therapeutics.