Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized by progressive cardiac conduction impairment, arrhythmias and sudden death. Mexiletine is a sodium-channel blocker drug used in such patients for the treatment of myotonia, even if definitive proof of its safety over long-term follow-up is lacking OBJECTIVE: To assess the impact of mexiletine for treatment of neurological symptoms on the composite endpoint of significant ECG modification (new onset or worsening of atrioventricular or intraventricular conduction delay) and bradyarrhythmic complications requiring pacemaker implantation (advanced atrioventricular block, symptomatic sinus pause >3 s) METHODS: This retrospective longitudinal study included a series of consecutive patients with genetically confirmed DM1 evaluated in our Neurology and Cardiology Clinic from January 1 2011 to January 1 2020, who received a 200 mg twice daily (BID) dose of mexiletine. Patients with pacemaker, implantable cardioverter defibrillation, or severe conduction abnormality (PQ interval ≥230ms, complete bundle branch block or atrial fibrillation) at enrollment were excluded RESULTS: we included 18 mexiletine-treated patients and 68 mexiletine-free controls. Over a median follow-up of 53 months, the endpoint was reached by 4 (22%) mexiletine-treated patients and 23 (33%) non mexiletine-treated patients (logrank p=0.45). In 3 non mexiletine-treated patients, bradyarrhythmic complications requiring pacemaker implantation were observed. At multivariable univariable analysis, only the presence of mild conduction delay (first-degree AV block with PQ<230 ms or left anterior fascicular block) at baseline predicted the endpoint (HR=2.22, CI=1.04-4.76) CONCLUSION: Mexiletine, at dosage of 200 mg BID, is safe in patients with DM1 and no severe conduction abnormality.Copyright © 2020. Published by Elsevier Inc.