Background: Case Summary: A 76-year-old man with a prior bioprosthetic aortic valve replacement presented with at least 2 weeks of fatigue, generalized weakness, intermittent chills, and worsening dyspnea, along with approximately 8 kg of unintentional weight loss since the preceding summer; he remained afebrile. Blood cultures remained persistently negative. Transesophageal echocardiography revealed a > 3-cm vegetation, prosthetic valve dehiscence, severe paravalvular regurgitation, and periannular abscess. Despite empiric broad-spectrum antibiotics and urgent surgical evaluation, the patient deteriorated and suffered cardiac arrest. Whole-blood polymerase chain reaction testing collected during hospitalization returned positive for Discussion: Whipple endocarditis typically presents as culture-negative disease and often lacks systemic features, delaying recognition. This case highlights the diagnostic challenge posed by Take‐Home Message: Early PCR testing should be considered in culture-negative prosthetic endocarditis, as it may establish a diagnosis when conventional cultures and valve tissue are unavailable.