Accidental azygos vein cannulation during central venous access via the internal jugular vein is rare, occurring in approximately 0.7–1.2% of cases, but represents a potentially serious complication requiring prompt recognition and management. Misplacement typically occurs without resistance during advancement but is often characterized by poor venous return or difficulty aspirating blood. The risk is increased in patients with venous congestion or dilation, such as those with portal hypertension, congestive heart failure, or right heart strain, where the azygos vein may be enlarged. Complications of malposition include pleural effusion, pulmonary edema, chest wall abscess, dyspnea, chest or back pain, and, in severe cases, cardiac tamponade. Diagnosis can be challenging; while chest radiographs may suggest malposition, confirmation generally requires contrast-enhanced CT, fluoroscopy, or echocardiography. Management depends on catheter function and patient stability. Functional catheters may be repositioned into the superior vena cava, whereas non-functional or symptomatic catheters should be removed after excluding vascular perforation. When perforation is suspected, early consultation with vascular surgery or interventional radiology is essential to minimize the risk of hemorrhagic complications.