OBJECTIVES: This study sought to describe expected changes in a mirror-image prone electrocardiogram (ECG) compared with normal supine, including a range of cardiac conditions. BACKGROUND: Unwell COVID-19 patients are at risk of cardiac complications. Prone ventilation is recommended but poses practical challenges to acquisition of a 12-lead ECG. The effects of prone positioning on the ECG remain unknown. METHODS: 100 patients each underwent 3 ECGs: standard supine front (SF); prone position with precordial leads attached to front (PF); and prone with precordial leads attached to back in a mirror image to front (PB). RESULTS: Prone positioning was associated with QTc prolongation (PF 437 +/- 32 ms vs. SF 432 +/- 31 ms; p < 0.01; PB 436 +/- 34 ms vs. SF 432 +/- 31 ms; p = 0.02). In leads V1 to V3 on PB ECG, a qR morphology was present in 90% and changes in T-wave polarity in 84%. In patients with anterior ischemia, ST-segment changes in V1 to V3 on supine ECG were no longer visible on PB in 100% and replaced by an R wave in V1. Bundle branch block (BBB) remained detectable in 100% on PB, with left BBB appearing as right BBB on PB in 71% and QRS narrowing with qR in V1 for right BBB. ST-segment/T-wave changes in limb leads and arrhythmia detection were largely unaffected in PB. CONCLUSIONS: As expected, the PB ECG is unreliable for the detection of anterior myocardial injury but remains useful for ST-segment/T-wave abnormalities in limb leads, BBB detection, and rhythm monitoring. The prone ECG is a useful screening tool with diagnostic utility in COVID-19 patients who require prone ventilation.