Echocardiography may miss prosthetic heart valve (PHV) endocarditis which advocates for novel imaging techniques to improve diagnostic accuracy and patient outcome. The purpose of this study was to determine the complementary diagnostic value of cardiac computed tomography angiography (CTA) to the clinical routine workup including transthoracic and transesophageal echocardiography (TTE/TEE) in patients with suspected PHV endocarditis and its impact on patient treatment. A diagnostic prospective cross-sectional study was chosen as design. Besides clinical routine workup (including TTE/TEE), CTA was performed to assess its diagnostic accuracy and complementary diagnostic/therapeutic value. For the diagnostic accuracy, the reference standard was surgical findings or clinical follow-up. To determine the complementary diagnostic/therapeutic value an expert-panel was used as reference standard. Twenty-eight patients were included. CTA resulted in a major diagnostic change in six patients (21 %) mainly driven by novel detection of mycotic aneurysms by CTA. Furthermore, treatment changes occurred in seven patients (25 %) compared to clinical routine workup. Diagnostic accuracy of routine clinical workup plus CTA was superior to clinical routine workup alone for the detection of PHV endocarditis in general, vegetations and peri-annular extension. This study demonstrates that CTA and clinical workup including TTE and TEE are complementary in patients with PHV endocarditis. Therefore, CTA imaging has to be considered after clinical routine workup in patients with a high suspicion on PHV endocarditis.