The administration of propofol target-controlled infusion (TCI) for procedural sedation is standard in a range of hospital settings except for the Emergency Department (ED). Propofol TCI could be an alternative, safer way to provide procedural sedation in the ED compared with other methods of propofol administration. We compare the incidence of adverse events using propofol TCI compared with other methods of propofol administration. We conducted a systematic review of the literature from 1946 to January 2019 identifying studies that compared propofol TCI with other propofol regimens for procedural sedation in the adult population. Studies were assessed for risk of bias using the Cochrane Collaboration risk of bias tool. Seven articles were included. There was significant methodological heterogeneity in all aspects of study designs and definitions of adverse events which precluded a meta-analysis. A systematic review of the studies demonstrated fewer respiratory and cardiovascular adverse outcomes in three of the seven studies. It was not possible to determine if propofol TCI reduces the incidence of adverse events when compared with other sedating regimens using propofol using a descriptive systematic review of the relevant literature. Further research is required to compare the incidence of adverse events using propofol TCI for procedural sedation with other methods of administration in the ED. Future systematic reviews and meta-analysis comparisons would be aided by the use of standard adverse event reporting tools such as that of the Society of Intravenous Anaesthesia.