Infective endocarditis (IE) is a potentially life-threatening disease. Little is known about temporal trends in its prevalence in Germany. In 2009, recommendations for antibiotic prophylaxis were deescalated in the revised European Society of Cardiology guideline to include only patients at high risk of IE. We selected patients with the discharge diagnosis of IE based on the International Classification of Diseases code I33 in the nationwide database of the Federal Statistical Office of Germany. We identified 94,364 patients with a diagnosis of IE from January 2005 to December 2014. Mean prevalence was 11.6 per 100,000 citizens per year in this 10-year-period. The annual IE prevalence showed a continuous small increase from 2006 to 2010 (9.5 to 10.6 IE diagnoses per 100,000 citizens) and a larger increase from 2011 to 2014 (11.1 to 14.4 IE diagnoses per 100,000 citizens; linear regression: β 2.9, 95% confidence interval 1.1 to 4.6; p = 0.006). The prevalence of IE in Germany was lower compared to the United States but higher compared to England. Overall, 15,995 patients (17%) died in hospital. Case fatality rate after a diagnosis of IE remained largely constant from 2005 to 2014. In conclusion, the annual prevalence of IE continuously increased during the observed period with more pronounced trend after the revised 2009 European Society of Cardiology guideline.