The management of concomitant mitral valve (MV) disease in patients with hypertrophic cardiomyopathy (HCM) remains controversial. The 2020 American Heart Association/American College of Cardiology HCM guidelines recommend that MV replacement (MVR) at the time of myectomy should not be performed for the sole purpose of relieving outflow obstruction. At the national level, limited data exist on the surgical outcomes of MV repair/replacement in patients with HCM who underwent septal myectomy (SM). Hospitalizations of patients with HCM who underwent SM between 2005 and 2020 were identified using International Classification of Diseases, Ninth and Tenth Revision codes (International Classification of Diseases, Ninth and Tenth Revision Clinical Modification/ProcedureCoding System). The 3 comparison cohorts were SM alone, MV repair, and MVR with concomitant SM. After propensity matching, 2 cohorts, SM+MVR versus SM+MV repair, were studied for surgical outcomes. Demographic characteristics, baseline co-morbidities, procedural complications, inpatient mortality, length of stay, and cost of hospitalization were compared between the propensity-matched cohorts. A total of 16,797 SM procedures were identified from 2005 to 2020. Among them, 11,470 hospitalizations had SM alone (68.2%), SM+MVR was seen in 3,101 (18.4%), and SM+MV repair comprised 2,226 (13.2%). After propensity matching, the MVR and MV repair formed the matched cohorts of 1,857. There were no significant differences in the odds of cardiogenic shock (adjusted odds ratio [aOR] 0.88, 95% confidence interval [CI] 0.63 to 1.24, p=0.49), mechanical circulatory support requirement (aOR 0.58, 95% CI 0.37 to 0.90, p=0.015), stroke (aOR 1.27, 95% CI 0.81 to 1.99, p=0.29), and major bleeding (aOR 0.52, 95% CI 0.34 to 0.79, p=0.0026) between the comparison groups. MVR, compared with MV repair, was associated with a higher risk of procedural mortality (8.02% vs 3.18%, aOR 2.98, 95% CI 2.05 to 4.33, p <0.0001), complete heart block (16.36% vs 12.15%, aOR 1.76, 95% CI 1.44 to 2.12, p <0.0001), and the need for permanent pacemaker (16.39% vs 10.62%, aOR 1.83, 95% CI 1.41 to 2.38, p <0.0001). The total length of hospital stay and median hospitalization cost was higher in the MVR group. SM in HCM concomitant with MVR is associated with higher procedural mortality and in-hospital complication risk. These real-world data support the 2020 American Heart Association/American College of Cardiology guidelines that in patients who are candidates for surgical myectomy, MVR should not be performed as part of the operative strategy for relieving outflow obstruction in HCM.