Background: Small studies suggest that variations in plasma potassium (p-K) levels may affect cardiac contractile function. A substudy to the recently published POTCAST trial demonstrated short-term improvements in myocardial function in patients randomized to potassium-increasing treatment. However, the long-term effects of increasing p-K on cardiac function remain unclear. This study aimed to investigate whether treatment that increases p-K improves diastolic and systolic myocardial function as assessed by echocardiography during long-term follow-up in a Danish implantable cardioverter-defibrillator (ICD) cohort. Methods: The POTCAST trial randomized patients with an ICD (1:1) to either usual therapy (control group) or treatment with oral potassium supplements and/or mineralocorticoid receptor antagonists (high-normal potassium group). In this substudy, consecutive patients from both arms of the POTCAST trial were included. Echocardiography was performed at baseline and repeated after > 6 months for the current study to compare changes in left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), global constructive work (GCW), and diastolic parameters (E, e’, and E/e’) between the high-normal potassium and control groups. Results: A total of 289 patients (mean age, 58 ± 13.4 years; 77.5% male) were included in the study. The median follow-up time between baseline and follow-up echocardiography was 729 days (interquartile range, 511–986 days).From baseline to follow-up the high-normal potassium group had an increase in mean difference in p-K of 0.22 mmol/L (95% confidence interval [CI], –0.31 to –0.13; P < 0.001) compared to the control group. In the high-normal potassium group e’lat increased by 0.77 cm/sec (95% CI, 0.12–1.40; P = 0.020), and E/e’lat decreased by –1.15 (95% CI, –2.1 to –0.25; P = 0.013) on average compared to the control group. No significant differences were observed in changes in other diastolic parameters. For systolic function, no significant differences were found between groups in terms of change in LVEF (–0.6%; 95% CI, –2.17 to 1.02; P = 0.475), GLS (–0.26%; 95% CI, –0.8 to 0.4; P = 0.472), or GCW (–3.99 mmHg; 95% CI, –89.5 to 81.6; P = 0.927). Conclusions In contrast to previous short-term findings, when myocardial function was assessed by echocardiography, long-term potassium-increasing treatment led to only minor improvements in diastolic function in a contemporary Danish ICD cohort.