In this Chapter, a MATLAB-based approach is presented for compression of Electrocardiogram (ECG) data. The methodology employs in three different domains namely direct, transformed and parameter extraction methods. The selected techniques from direct ECG compression methods are TP, AZTEC, Fan, and Cortes. Moreover selected techniques from transformed ECG compression methods are Walsh Transform, DCT, and Wavelet transform. For each of the technique, the basic implementation of the algorithm was explored, and performance measures were calculated. All 48 records of MIT-BIH arrhythmia ECG database were employed for performance evaluation of various implemented techniques. Moreover, based on requirements, any basic techniques can be selected for further innovative processing that may include the lossless encoding.