Traditionally, late-stage empyema is managed with open chest surgery performed via thoracotomy. More recently, minimally invasive approach has been shown to be a safe alternative, and may be associated with improved post-operative morbidity. We propose that single-incision thoracoscopic surgery (SITS) may result in further benefits in post-operative outcomes in appropriate patients. Here, we present the case of a 75-year-old male, immunosuppressed due to treatment for rheumatoid arthritis, with chronic anemia and thrombocytopenia due to myelodysplastic syndrome, who had a two-month history of frequent hospital admissions for exertional dyspnea and malaise. After completing several courses of antibiotics for community acquired pneumonia, the patient developed a parapneumonic empyema. He underwent decortication, drainage and debridement of empyema via a minimally invasive, single-incision approach. By post-operative day two, all chest tubes were removed and the patient was deemed medically appropriate for discharge. This case demonstrates that, in the experienced surgeon's hands, a minimally invasive and indeed, single incision approach, can result in rapid resolution of late-stage empyema and favorable post-operative outcomes. This may prove particularly beneficial in those with high perioperative risk.