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The electrocardiogram (ECG) is one of the most important techniques for heart disease diagnosis. Many traditional methodologies of feature extraction and classification have been widely applied to ECG analysis. However, the effectiveness and efficiency of such methodologies remain to be improved, and much existing research did not consider the separation of training and testing samples from the same set of patients (so called inter-patient scheme). To cope with these issues, in this paper, we propose a method to classify ECG signals using wavelet packet entropy (WPE) and random forests (RF) following the Association for the Advancement of Medical Instrumentation (AAMI) recommendations and the inter-patient scheme. Specifically, we firstly decompose the ECG signals by wavelet packet decomposition (WPD), and then calculate entropy from the decomposed coefficients as representative features, and finally use RF to build an ECG classification model. To the best of our knowledge, it is the first time that WPE and RF are used to classify ECG following the AAMI recommendations and the inter-patient scheme. Extensive experiments are conducted on the publicly available MIT–BIH Arrhythmia database and influence of mother wavelets and level of decomposition for WPD, type of entropy and the number of base learners in RF on the performance are also discussed. The experimental results are superior to those by several state-of-the-art competing methods, showing that WPE and RF is promising for ECG classification.