Acalabrutinib, a next-generation Bruton's tyrosine kinase inhibitor (BTKi), associates with dramatic efficacy against B-cell malignancies. Recently, unexplained ventricular arrhythmias (VAs) with next-generation BTKi-therapy have been reported. Yet, whether acalabrutinib associates with VAs in long-term follow-up is unknown. Leveraging a large cohort of 290 consecutive B-cell malignancy patients treated with acalabrutinib from 2014-2020, we assessed the incidence of VAs. The primary endpoint was incident VA-development, including ventricular fibrillation, ventricular tachycardia, and symptomatic premature ventricular-contractions. Probability Scores were assessed to determine likelihood of acalabrutinib-association. Incident rates as a function of time-on-therapy were calculated. Weighted average observed incidence rates were compared to expected population rates using relative risks. Absolute excess risk (AER) for acalabrutinib-associated VAs was estimated. Over 1,063 person-years of follow-up, there were 8 cases of incident VAs, including 6 in those without coronary-disease (CAD) or heart-failure (HF), and 1 sudden death; median time-to-event was 14.9 months. Among those without prior ibrutinib-use, CAD, or HF, the weighted average incidence was 394 per 100,000 person-years compared to a reported incidence of 48.1 among similar-aged non-BTKi-treated subjects (RR 8.2, P<0.001; AER 346). Outside of age, no cardiac or electrocardiographic variables associated with VA-development. Collectively, these data suggest VAs may be a class-effect of BTKi-therapies.