Perioperative interventions aimed at decreasing costs and improving outcomes have become increasingly popular in recent years. Anesthesiologists are often faced with a choice among different treatment strategies with little data available on the comparative cost-effectiveness. We performed a systematic review of the English language literature between 1980 and 2014 to identify cost-effectiveness analyses of anesthesiology and perioperative medicine interventions. We excluded interventions related to critical care or pediatric anesthesiology, and articles on interventions not normally ordered or performed by anesthesiologists. Of the >5000 cost-effectiveness analyses published to date, only 28 were applicable to anesthesiology and perioperative medicine and met inclusion criteria. Multidisciplinary interventions were the most cost-effective overall; 8 of 8 interventions were "dominant" (improved outcomes, reduced cost) or cost-effective, including accelerated, standardized perioperative recovery pathways, and perioperative delirium prevention bundles. Intraoperative measures were dominant in 3 of 5 cases, including spinal anesthesia for benign abdominal hysterectomy. With regard to prevention of perioperative infection, methicillin-resistant Staphylococcus aureus (MRSA) decolonization was dominant or cost-effective in 2 of 2 studies. Three studies assessing various antibiotic prophylaxis regimens had mixed results. Autologous blood donation was not found to be cost-effective in 5 of 7 studies, and intraoperative cell salvage therapy was also not cost-effective in 2 of 2 reports. Overall, there remains a paucity of cost-effectiveness literature in anesthesiology, particularly relating to intraoperative interventions and multidisciplinary perioperative interventions. Based on the available studies, multidisciplinary perioperative optimization interventions such as accelerated, standardized perioperative recovery pathways, and perioperative delirium prevention bundles tended to be most cost-effective. Our review demonstrates that there is a need for more rigorous cost-effective analyses in many areas of anesthesiology and that anesthesiologists should continue to lead collaborative, multidisciplinary efforts in perioperative medicine.