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To study the association between Streptococcus bovis (S. bovis) endocarditis and advanced colorectal neoplasia.This was a case–control study of patients with S. bovis endocarditis undergoing colonoscopic evaluation. Patients were matched 1:20 with controls by gender and age (±2 years) from a large screening colonoscopy database. The baseline, colonoscopic and clinicopathological characteristics of patients with S. bovis endocarditis were analyzed.From 1996 to 2010, 18 adult patients with S. bovis bacteremia were identified, of whom 10 with infective endocarditis (IE) underwent colonoscopic evaluation. Endocarditis involved a native or prosthetic valve in six and four of those patients, respectively. All 10 patients recovered without recurrence of IE (mean follow-up duration 49.6 months). None had a concurrent or preceding history of colon disease and only one had subclinical chronic liver disease. Advanced neoplasia, defined as the presence of polyps ≥1 cm (n = 6), villous histology (n = 3), high-grade focal dysplasia (n = 1) or cancer (n = 1), was found under colonoscopy in 6 of the 10 cases (60.0%) compared with 13/200 (6.5%) matched controls (OR 21.6, 95% CI 5.4–86.1, P < 0.0001).S. bovis endocarditis is strongly associated with the presence of advanced colorectal neoplasia. In the absence of any contraindication, colonoscopic examination is strongly recommended in patients with endocarditis. The exact pathophysiological mechanisms underlying this association and the predilection for S. bovis bacteremia in patients with advanced colonic neoplasia remain unclear.