Cytoprotective and organoprotective pentadecapeptide BPC 157 demonstrated particular beneficial cardiovascular effects (Curr Pharm Des. 2014 ; 20(7):1121-1125). Antiarrhythmic effects counteracted digoxin toxicity (Regul Pept. 2009 ; 156(1-3):83-89), major blood vessel occlusions (Biomedicines 2021, 9, 1029 ; 2021, 9, 609 ; 2021, 9, 792) and lidocaine toxicity (Emerg Med Int. 2020 ; 2020:6805354). Now, we reveal, by BPC 157, mitigation of hemodynamic and ECG disturbances of sotalol, a class III antiarrhythmic with non- selective beta-blocking activity. Albino Wistar rats received sotalol (80mg/kg, intragastrically), and at 5 min thereafter were treated with saline or BPC 157 (10ng/kg, intragastrically. Seven standard and one precordial ECG leads were recorded (baseline ; after application of sotalol ; and 10, 30, 90, 120 and 150 minutes after application of sotalol). Heart rate, QRS complex, PR and QT intervals were analyzed. Corrected QT intervals (QTc) were calculated according to Fridericia formula. Baseline ECG readings included average heart rate of 275.5 ± 25 bpm, average PR 54.8 ± 3.4 ms, average QRS complex 25.0 ± 4.23 ms and average QTc 166 ± 9.7 ms. Sotalol caused bradycardia (245 ± 23.5 bpm), PR prolongation (57.3 ± 2.7 ms), QRS widening (26.3 ± 3.2 ms), and QTc prolongation (173 ± 9.1 ms), measured 10 minutes after application. In BPC 157 treated animals (5 minutes after BPC-157 application, 10 minutes after sotalol application), these effects were attenuated (heart rate 306 ± 31.7 bpm, average PR 52.3 ± 1.6 ms, average QRS 23.7 ± 5.4 ms and average QTc 159 ± 21.2 ms). This attenuation was lost in later measurements, for QRS - 25 minutes after BPC 157 application, for frequency after 55 minutes, for PR after 115 minutes and for QTc after 145 minutes. In animals treated with sotalol, an increase in superior sagittal sinus pressure (10 ± 5 mmHg), as well as an increase in portal vein (17 ± 4 mmHg) and inferior caval vein pressures (12 ± 6 mmHg) were noted, along with the decrease in abdominal aortic pressure (53 ± 10 mmHg). These effects were attenuated in BPC treated animals (-1 ± 1 mmHg for superior sagittal sinus, 7 ± 1 mmHg in portal vein, 5 ± 1 mmHg in inferior caval vein, and 81 ± 7 mmHg in abdominal aorta). In conclusion, BPC 157 attenuated deleterious hemodynamic effects of sotalol while the effects on the ECG parameters were also noted, although not long lasting, supporting the view of BPC-157 as a rapid-acting protective agent.