Background/Objectives: Timely diagnosis of infective endocarditis (IE) remains a significant challenge, and IE poses significant morbidity and mortality. Modified Duke criteria (MDC) are used for the clinical evaluation and diagnosis of IE, but their current use is dichotomous. There are no studies that associate the amount of positive MDC with the patient’s outcome. This study intends to analyze whether the amount of MDC on initial presentation can be used for prognostic assumptions. Methods: We conducted a retrospective data analysis on patients with confirmed and suspected IE who were treated at the Department of Internal Medicine II at Ulm University Heart Center from December 2009 to December 2019. Univariable and multivariable logistic regression models were used to find correlations between 90-day mortality and the number of MDC. Results: 130 patients with confirmed IE were included in the analysis. Less minor MDC (OR 1.718; 95%-CI 1.096–3.268; p = 0.022) and a history of coronary artery disease (OR 4.711; 95%-CI 1.791–12.393; p = 0.002) were independently associated with higher 90-day mortality in patients with ultimately confirmed IE. Fewer minor MDC on presentation were associated with later diagnosis (b 2.341; 95%-CI 0.312–4.370; p = 0.024) and antibiotic therapy (b 2.953; 95%-CI 0.82–5.084; p = 0.007) for IE. Conclusions: Early diagnosis of IE is essential for favorable outcomes. Fewer minor MDC on initial presentation may lead to delayed diagnosis, antibiosis, and worse outcomes.