Background: Inappropriate sinus tachycardia (IST) is a rare clinical disorder characterized by an elevated resting heart rate and an exaggerated rate response to exercise or autonomic stress. Pharmacologic therapy and catheter ablation are considered first-line treatments for IST but can yield suboptimal relief of symptoms. The results of surgical ablation at our center were reviewed for patients with refractory IST. Methods: Between 1987 and 2018, 18 patients underwent surgical sinoatrial (SA) node isolation for treatment-refractory IST. All 18 patients had previously failed pharmacologic therapy, and 15 patients had failed catheter ablation of the SA node. Results: Ten patients underwent a median sternotomy, and 8 patients underwent a minimally invasive right thoracotomy. The SA node was isolated with the use of surgical incisions, cryoablation, or bipolar radiofrequency ablations. Sinus tachycardia was eliminated in 100% of patients in the immediate postoperative period. Long-term follow-up data were available for 17 patients, with a mean follow-up of 11.4 ± 7.9 years. At last follow-up, 100% of patients were free from recurrent symptomatic IST. More than 80% of patients were completely asymptomatic, whereas 3 patients reported occasional palpitations. Four patients were on β-blockers, and 5 patients required subsequent pacemaker implantation. All 8 patients who underwent minimally invasive isolation were in normal sinus rhythm at last follow-up, and only 1 patient complained of palpitations. Conclusions: Surgical isolation of the SA node is a feasible treatment for IST refractory to pharmacologic therapy and catheter ablation. A minimally invasive surgical approach offers a less morbid alternative to traditional median sternotomy.