Therapy for pyothorax, or pleural empyema, has not been described for large felids. This case describes the successful treatment of pyothorax in a captive, large felid. A 15-yr-old multiparous, female Amur tiger (Panthera tigris altaica) presented with nonspecific clinical signs caused by an insidious onset of pyothorax. Management of pyothorax cases in companion animals often involves thoracostomy tube placement with recurrent drainage of the pleural cavity, intensive supportive care, and monitoring. In this case, conservative management was elected because hospitalization was not a viable option. Thoracocentesis was performed to drain as much fluid from the chest cavity as possible, yielding more than 1.3 L. Corynebacterium sp. and unidentified anaerobic gram-positive cocci were cultured. Treatment included cefovecin subcutaneously, oral antibiotic therapy with clindamycin and marbofloxacin, meloxicam, and restricted exercise by minimizing access to the main exhibit. Significant improvement was noted clinically and radiographically 6 wk later, and no relapses were noted in the following weeks. An examination 11.5 mo later confirmed resolution.