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This paper presents a complete study of wide-area wireless ECG transmission for real-time cardiac tele-monitoring taking into account both technical and clinical aspects, in order to provide recommendations for real-time monitoring considering both channel parameters and the tolerance of cardiologists to the effects of interruptions introduced during transmission. By using extensive wireless simulated scenarios, the compressed ECG signal is monitored on reception. A new protocol [real-time ECG transmission protocol, reliable ECG transmission protocol (RETP)] is used to perform the retransmissions of erroneous packets, introducing a monitoring buffer that mitigates possible negative effects. Assessments by cardiologists have shown that the maximum percentage of time for which the monitoring process could be stopped without their feeling uncomfortable is around 15% with a maximum monitoring delay of 3 or 4 s, depending on the scenario in question. Taking into account these values and the results obtained in the simulations, it is a straightforward step to obtain working areas for the wireless channel parameters where transmission is not recommended from a clinical point of view.