Background Short QT syndrome ( SQTS ) is a rare inheritable disease associated with sudden cardiac death. Data on long-term outcomes of families with SQTS are limited. Methods and Results Seventeen patients with SQTS in 7 independent families (48% men; median age, 42.4 years; corrected QT interval, 324.9±40.8 ms) were followed up for 13.5±2.5 years. A history of sudden cardiac death was documented in 71% of families. A large number of them showed sudden cardiac deaths at a younger age, with a predominance of men (67%). Five patients had syncope (29%) and 9 (53%) had atrial fibrillation or atrial flutter. An SQTS -related gene was found in 76% of the patients as follows: KCNH 2 ( SQTS 1) in 4, CACNA 1C ( SQTS 4) in 3, and CACN b2 ( SQTS 5) in 6. Five patients (29%) received an implantable cardioverter-defibrillator and 5 patients received long-term prophylaxis with hydroquinidine. During follow-up, 1 patient received an appropriate implantable cardioverter-defibrillator shock attributable to ventricular fibrillation. The patient received no further implantable cardioverter-defibrillator shocks after treatment with hydroquinidine. Conclusions The risk of sudden cardiac death in SQTS families is high. However, after appropriate risk assessment and individualized treatment options (hydroquinidine and/or implantable cardioverter-defibrillator), the long-term outcome is relatively benign when patients are seen at a reference center.