The use of personal protective equipment (PPE) is a cornerstone of infection prevention and control guidelines and was of increased importance during the COVID-19 pandemic. Adherence with prescribed guidelines for the use of PPE and their applicability to the working practices of staff in general practitioner (GP) and ambulance settings have been a growing concern. The aim of this rapid review was to assess the barriers, facilitators, and potential adverse outcomes of the use of PPE in these specific settings. Included studies were published from 2020 to November 2022. We identified four systematic reviews, a rapid review, a retrospective chart review, and a prospective quantitative survey study. Outcome measures were broadly focused on physical adverse outcomes from the use of PPE, but also included barriers and facilitators to the use of PPE in varied healthcare settings. The five reviews covered a broad range of health and care settings, which included GP and ambulance settings, but not as a specific focus. Both the retrospective chart review and the prospective survey study took place in an ambulance or emergency response setting. Overall confidence in the body of evidence is low. Extended use of PPE is associated with an increased occurrence of adverse physiological events, such as pressure ulcers and de novo headaches. Evidence indicates that adherence with PPE guidance is primarily influenced by organisational communication and workplace cultures. In ambulance settings, adherence may also be affected by dispatch codes and indicative symptoms reported during the initial call. Policy implications: As there is evidence to suggest that usage of PPE increases risk of adverse effects in healthcare workers, this should be at the forefront of considerations when developing or reviewing new and existing infection prevention and control measures. If new policy regarding the use and implementation of PPE is to be developed, effective communication and dissemination should be a priority, as this was identified as a barrier to adherence. This review has identified a significant paucity of evidence in the settings of interest and is reliant on examining evidence that represents a large variety of health and care settings. It is important to acknowledge there may be some issues specific to Ambulance and GP settings that are not covered by this review. This does impact the validity of this reviews conclusions.