Abstract: Intravascular ultrasound (IVUS) represents a powerful imaging technique to explore coronary vessels and to study their morphology and histologic properties. In this paper, we characterize different tissues based on Radio Frequency, texture-based, slope-based, and combined features. To deal with the classification of multiple tissues, we require the use of robust multi-class learning techniques. In this context, we propose a strategy to model multi-class classification tasks using sub-classes information in the ECOC framework. The new strategy splits the classes into different subsets according to the applied base classifier. Complex IVUS data sets containing overlapping data are learnt by splitting the original set of classes into sub-classes, and embedding the binary problems in a problem-dependent ECOC design. The method automatically characterizes different tissues, showing performance improvements over the state-of-the-art ECOC techniques for different base classifiers and feature sets.