Background: Although current evidence points to the possible prognostic value of electrocardiographic (ECG) findings for in-hospital mortality of COVID-19 patients, most of these studies have been performed on a small sample size. In this study, our aim was to investigate the ECG changes as prognostic indicators of in-hospital mortality. Methods: In a retrospective cohort study, the findings of the first and the second ECGs of COVID-19 patients were extracted and changes in the ECGs were examined. Any abnormal finding in the second ECG that wasn't present in the initial ECG at the time of admission was defined as an ECG change. ECGs were interpreted by a cardiologist and the prognostic value of abnormal ECG findings for in-hospital mortality of COVID-19 patients was evaluated using multivariate analysis and the report of the relative risk (RR). Results: Data of the ECGs recorded at the time of admission were extracted from the files of 893 patients; likewise, the second ECGs could be extracted from the records of 328 patients who had an initial ECG. The presence of sinus tachycardia (RR = 2.342; p <0.001), supraventricular arrhythmia (RR = 1.688; p = 0.001), ventricular arrhythmia (RR = 1.854; p = 0.011), interventricular conduction delays (RR = 1.608; p = 0.009), and abnormal R wave progression (RR = 1.766; p = 0.001) at the time of admission were independent prognostic factors for in-hospital mortality. In the second ECG, sinus tachycardia (RR = 2.222; p <0.001), supraventricular arrhythmia (RR = 1.632; p <0.001), abnormal R wave progression (RR = 2.151; p = 0.009), and abnormal T wave (RR = 1.590; p = 0.001) were also independent prognostic factors of in-hospital mortality. Moreover, by comparing the first and the second ECGs, it was found that the incidence of supraventricular arrhythmia (RR = 1.973; p = 0.005) and ST segment elevation/depression (RR = 2.296; p <0.001) during hospitalization (ECG novel changes) are two independent prognostic factors of in-hospital mortality in COVID-19 patients. Conclusion: Due to the fact that using electrocardiographic data is easy and accessible and it is easy to continuously monitor patients with this tool, ECGs can be useful in identifying high-risk COVID-19 patients for mortality.