Background: The frequency and temporal trend in the prevalence of arrhythmias and associated in-hospital outcomes in patients with sickle cell disease (SCD) have never been quantified. Methods: Our study cohort of SCD patients and sub-types of arrhythmias were derived from the 2010-2014 National Inpatient Sample using relevant diagnostic codes. The frequency and trends of arrhythmia and odds of inpatient mortality were measured. Results: A total of 891 450 hospitalized SCD patients were identified, of which, 55 616 (6.2%) patients experienced arrhythmias. The SCD cohort with arrhythmia demonstrated higher all-cause mortality (2.7% vs 0.4%; adjusted OR 2.53, 95% CI 2.15-2.97, P <.001), prolonged hospital stays (6.9 vs 5.0 days) and higher hospital charges ($53 871 vs $30 905) relative to those without arrhythmias (P <.001).The frequency of supraventricular arrhythmia (AFib, SVT, and AF) and ventricular arrhythmia (VFib and VT) were 1893 and 362 per 100 000 SCD-related admissions, respectively. Unspecified arrhythmias (4126) were seen most frequently followed by AFib (1622) per 100 000 SCD-related admissions. From 2010 to 2014, the frequency of any arrhythmias and atrial fibrillation in hospitalized SCD patients relatively increased by 29.6% and 38.5%, respectively. There was nearly a twofold (2.4% in 2010 to 5.0% in 2014) increase in the frequency of arrhythmia among patients aged <18 years. The frequency of arrhythmias in hospitalized male and female SCD patients relatively increased by 28.8% and 31.4%, respectively (Ptrend <.001). Conclusions: The frequency of arrhythmias among SCD patients is on the rise with worse hospitalization outcomes, including higher in-hospital mortality and higher resource utilization as compared to those without arrhythmias.