The increasing volume of office-based medical and surgical procedures has fostered the emergence of office-based anesthesia (OBA), a subspecialty within ambulatory anesthesia. The growth of OBA has been facilitated by numerous trends, including innovations in medical and surgical procedures and anesthetic drugs, as well as improved provider reimbursement and greater convenience for patients. There is a lack of randomized controlled trials to determine how office-based procedures and anesthesia affect patient morbidity and mortality. As a result, studies on this topic are retrospective in nature. Some of the early literature broaches concerns about the safety of office-based procedures and anesthesia. However, more recent data have shown that care in ambulatory settings is comparable to hospitals and ambulatory surgery centers, especially when offices are accredited and their proceduralists are board-certified. Office-based suites can continue to enhance the quality of care that they deliver to patients by engaging in proper procedure and patient selection, provider credentialing, facility accreditation, and incorporating patient safety checklists and professional society guidelines into practice. These strategies aiming at patient morbidity and mortality in the office setting will be increasingly important as more states, and possibly the federal government, exercise regulatory authority over the ambulatory setting. We explore these trends, their implications for patient safety, strategies for minimizing patient complications and mortality in OBA, and future developments that could impact the field.