Background. Mediastinoscopy (MED) and endobronchial ultrasonography with transbronchial needle aspiration (EBUS-TBNA) have similar accuracy for mediastinal lymph node sampling (MLNS). The threatened financial and environmental sustainability of our health care system mandate that surgeons consider cost and environmental impact in clinical decision making of similarly effective procedures. We performed a cost and waste comparison of MED versus EBUS-TBNA for MLNS to raise awareness of the financial and environmental implications of our practices. Methods. We conducted a retrospective review of outpatients who underwent MLNS under general anesthesia in the OR with MED or EBUS-TBNA (September 2007 to December 2009). We analyzed direct costs based on hospital charges, calculated expected payment using a decision support model, and profit margins (modeled expected payment-direct costs). Our waste comparison was measured in kilograms of solid waste per case. Results. We performed MLNS in 148 patients (89 EBUS-TBNA, 39 MED, 20 EBUS + MED). Direct costs were lower for MED ($2,356) compared with EBUS-TBNA ($2,503), whereas expected payment was greater (MED, $3,449; EBUS-TBNA, $3,249), resulting in a profit margin that was $347 greater for MED. The amount of solid waste for each MED was 1.8 kg versus 0.5 kg for EBUS-TBNA. Conclusions. MED costs less than EBUS-TBNA in the OR setting but generates 3.6 times the amount of EBUS-TBNA waste. The cost of EBUS-TBNA may improve by performance in the endoscopy suite, and surgical pack revision could reduce the amount of MED solid waste. This comparison sets the stage for sophistication of our clinical decision making, taking into consideration the major threats to our health care system.