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Background: The association of infective endocarditis (IE) with spondylodiscitis (SD) was first reported in 1965, but few data are available about this issue. This study aimed to evaluate the prevalence of SD in patients with IE, and to determine the clinical features and the prognostic impact of this association., Methods: We retrospectively analysed 363 consecutive patients admitted to our Department with non-device-related IE. Radiologically confirmed SD was revealed in 29 patients (8%). Long-term follow-up (average: 3 years) was obtained by structured telephone interviews; in 95 cases (13 of whom had been affected by SD), follow-up echocardiographic evaluation was also available., Results: At univariable analysis, the combination of IE with SD was associated with male gender (p = 0.017), diabetes (p = 0.028), drug abuse (p = 0.009), Streptococcus Viridans (p = 0.009) and Enterococcus (p = 0.015) infections. At multivariable analysis, all these factors independently correlated with presence of SD in patients with IE. Mortality was similar in patients with and without SD. IE relapses at 3 years were associated with the presence of SD (p = 0.003), Staphylococcus aureus infection (p < 0.001), and drug abuse (p < 0.001) but, at multivariable analysis, only drug abuse was an independent predictor of IE relapses (p < 0.001; HR 6.8, 95% CI 1.6-29). At echocardiographic follow-up, SD was not associated with worsening left ventricular systolic function or valvular dysfunction., Conclusions: The association of IE with SD is not rare. Hence, patients with IE should be screened for metastatic infection of the vertebral column, especially if they have risk factors for it. However, SD does not appear to worsen the prognosis of patients with IE, either in-hospital or long-term.