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Aims  Mitral annular calcification (MAC) has been associated with adverse outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) but has been investigated in isolation of co-existent mitral regurgitation or mitral stenosis, which may represent important confounders. This study sought to investigate the effect of MAC with and without concomitant mitral valve disease (MVD) on clinical outcomes in patients treated with TAVR. Methods and results  Computed tomography (CT) and echocardiographic data in consecutive TAVR patients enrolled into a prospective registry were categorized according to presence or absence of severe MAC and significant MVD, respectively. A total of 967 patients with adequate CT and echocardiography data were included between 2007 and 2017. Severe MAC was found in 172 patients (17.8%) and associated with MVD in 87 patients (50.6%). Compared to TAVR patients without severe MAC or MVD, all-cause mortality at 1 year was significantly increased among patients with severe MAC in combination with MVD [adjusted hazard ratio (HRadj): 1.97, 95% confidence interval (CI): 1.12–3.44, P = 0.018] and patients with isolated MVD (HRadj: 2.33, 95% CI: 1.56–3.47, P < 0.001), but not in patients with isolated severe MAC in the absence of MVD (HRadj: 0.52, 95% CI: 0.21–1.33, P = 0.173). Conclusion  We found no effect of isolated MAC on clinical outcomes following TAVR in patients with preserved mitral valve function. Patients with MVD had an increased risk of death at 1 year irrespective of MAC.