Objective Pericardiocentesis is a well-known procedure commonly performed by either image-guided intervention or surgical approaches. Computed tomography (CT)-guided pericardiocentesis is not widely used, but provides certain advantages. In the article we will discuss our technique of CT-guided therapeutic pericardiocentesis, including advantages and disadvantages, patient selection, possible approaches, and complications. Methods The retrospective study included 121 therapeutic pericardial drainages performed under CT guidance. Demographic data of the patients, entry site, and needle orientation were recorded. Procedure complications and their significance were analyzed. Results One hundred and twenty-one pericardial drainages with catheter insertion were performed under CT guidance on 119 patients presenting with clinically significant pericardial effusion. The most common approach was at the left anterior chest wall. The rate of minor complications was 5.8%, no major complications occurred. Conclusions Therapeutic pericardiocentesis can be obtained under CT guidance in a safe and effective manner. Recommendations for building a patient-centered protocol with an interdisciplinary team are discussed. Patient selection, procedural guidance, and lessons to avoid complications are reviewed.