BACKGROUND: Unexplained sudden death is common among patients with sickle cell diseases (SCD). QTc prolongation is a risk factor for fatal arrhythmias among adults. This study sought to identify the predictors for QTc prolongation and determine whether QTc prolongation is associated with increased mortality in patients with SCD. METHODS: We reviewed the electrocardiograms (EKG) and the transthoracic echocardiograms (TTE) of 140 consecutive adults (>18 years) with SCD from October 1996 to January of 2012. QTc prolongation was categorized into three gender-specific categories based on previous publications. Stepwise regression was performed to evaluate QTc interval and mortality as dependent variables. Hemolytic burden as reflected in laboratory evaluation, diastolic, and systolic TTE variables were included in this model. RESULTS: In a stepwise regression analysis, only increased tricuspid regurgitant jet velocity (TRV) (r = 0.483, P = 0.015) had a significant association with QTc interval. Among 49 (35%) patients, the QTc interval was persistently prolonged (PP) (>450 ms in men, >470 ms in women). Twenty-one patients (15%) died over 9 years of follow-up. PP QTc was associated with increased mortality (HR; 8.3 with 95% CI: 2.8-24.6, P < 0.001) compared with normal QTc. In stepwise regression analysis, along with increased TRV (P = 0.005) and acute chest syndrome (P < 0.001), prolonged QTc (P = 0.004) was independently associated with increased mortality. CONCLUSION: Prolonged QTc among the patients with SCD is an independent risk factor for increased mortality.