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Septal myectomy remains the criterion standard for the treatment of patients with hypertrophic obstructive cardiomyopathy refractory to medical therapy. There have been few reports of minimally invasive approaches. This study compared a minimally invasive septal myectomy performed at our institution with the traditional full-sternotomy approach.Patients receiving a stand-alone septal myectomy were retrospectively reviewed from November 1999 to December 2016 (N = 120). Patients were stratified by surgical approach: traditional full sternotomy (n = 34) and ministernotomy (n = 86). Preoperative and perioperative variables were compared as well as follow-up symptomatic and echocardiographic outcomes.Both groups had a significant decrease in New York Heart Association class heart failure symptoms (P < 0.001). At a mean ± SD follow-up time of 2.0 ± 3.4 years, postoperative New York Heart Association class distribution was similar between ministernotomy and full sternotomy (P = 0.684). Follow-up resting left ventricular outflow tract gradient was also similar between ministernotomy and full sternotomy (11 mm Hg ± 15 vs 9 mm Hg ± 13, P = 0.381). Perioperatively, ministernotomy was not significantly different from full sternotomy in median cardiopulmonary bypass time (81 minutes vs 78 minutes, P = 0.101) but had a slightly longer median cross-clamp time (39 minutes vs 35 minutes, P = 0.017). Major complications were similar in the two groups. There was one 30-day mortality in the full-sternotomy group, but no in-hospital deaths.Septal myectomy performed using a minimally invasive approach has similar outcomes to the criterion standard operation done through a full sternotomy. It represents a feasible option for patients with hypertrophic obstructive cardiomyopathy unresponsive to medications.