Abstract Introduction There is scarce evidence regarding the optimal medical treatment of patients with heart failure and recovered LVEF. To date, no study has analyzed the efficacy of maintaining neurohormonal blockade in patients with arrhythmia-induced cardiomyopathy (AiCM) after LVEF normalization. Purpose The aim of this study is to analyze impact of pharmacological treatment for heart failure in preventing heart failure relapse after myocardial recovery in AiCM. Methods We analyze data from a single-center cohort of 200 patients admitted for heart failure and ventricular dysfunction initially attributed to AiCM between 2008 and 2020. Myocardial recovery was defined as an improvement in LVEF up to > = 50% (complete recovery) or an increase of > = 10% up to a value of LVEF >= 40% (partial recovery). Heart failure relapse was defined as a decrease in LVEF to <50% in those with previous complete recovery or a decrease of > = 10% in patients with partial recovery, unplanned Emergency Department (ED) visit or hospital admission for heart failure. As drug prescriptions are not constant over follow up, changes in medication have been recorded and time varying covariates were used for statistical analysis. A Fine and Gray competing-risk multivariate regression was performed, adjusting for initial LVEF at admission, degree of myocardial recovery (complete or partial), presence of underlying cardiomyopathy and age, considering death as competing risk. Results Over a median of 6.14 years, most of the patients had a complete myocardial recovery (n = 164; 82.0%). 24 patients (12%) had partial recovery and 12 patients (6.0%) did not show significant improvement in ventricular function. At the moment of myocardial recovery, ACEI/ARB/ARNI were prescribed in 160 patients (85.11%); beta-blockers in 170 (90.43%); ARB in 112 (59.57%); iSGLT2 in 8 (4.26%); antiarrhythmic drugs in 75 (39.89%) and Digoxin in 40 (21.28). From 188 patients with initial LVEF recovery, 64 (34.04%) had a relapse of systolic dysfunction. 65 patients (34.57%) required unplanned Emergency Department (ED) visits and 40 patients (21.28%) needed hospital admission for heart failure. Maintenance of ACEI/ARB/ARNI and beta-blockers after myocardial recovery was associated with a significant lower risk of HF relapse [sHR 0.43 (95% CI 0.26 - 0.73), p 0.002 for ACEI/ARB/ARNI]; [sHR 0.52 (95% CI 0.29 - 0.92), p 0.025 for beta-blockers]. ARM was associated with a non-significant lower risk of HF relapse [sHR 0.67 (95% CI 0.42 - 1.09), p 0.093]. Treatment with antiarrhythmic drugs [sHR 0.90 (95% CI 0.54 - 1.51), p 0.696] and Digoxin [sHR 0.90 (95% CI 0.54 - 1.51), p 0.696] did not show benefit in this study. Conclusions Maintenance of ACEI/ARB/ARNI and beta-blockers after myocardial recovery was associated with a significant lower risk of HF relapse after myocardial recovery in patients with AiCM.Risk of HF relapse - ACEI ARB ARNIRisk of HF relapse - BetaBlockers