Introduction Mechanical ventilation via an artificial airway can impede cough, predisposing the critically ill patient to retained secretions and an increased risk of respiratory complications. Physiotherapeutic techniques aimed at mobilising secretions and optimising airway clearance are often relied upon in this cohort. Mechanical Insufflation-Exsufflation (MI-E) is a cough augmentation device that utilises positive pressure, followed by a rapid switch to negative pressure, to simulate a cough and aid sputum clearance from proximal airways. To date, MI-E has been widely researched in the neuromuscular population, with emerging use in the critically ill. However, adverse effects associated with MI-E in intubated populations remains unknown. The aim of this review was to report on the incidence of adverse events associated with MI-E in acutely invasively ventilated critically ill patients. Methods An electronic search of online databases was conducted using AMED, CINAHL, Cochrane Library, EMBASE, MEDLINE, SPORTDiscuss and Web of Science. Additionally, the reference lists of relevant articles were hand searched for eligible studies. Studies including adult subjects (>18 years) who were invasively ventilated and receiving MI-E were deemed eligible for inclusion. The outcome of interest was adverse events. Studies were excluded if they were in a paediatric population, not written in English language and were editorials or conference papers. Quality was assessed using the Critical Skills Appraisal Programme tool. Results A total 77 citations were identified, five of which met the inclusion criteria: three randomised crossover studies, one randomised parallel-group open label trial and one case series (278 participants in total). All studies applied MI-E followed by endotracheal or tracheal suction. Insufflation and exsufflation pressures ranged from +30 to +50cmH2O and -30 to -50cmH2O across studies. Only two studies pre-defined an adverse event. Common reported measures included heart rate, systolic and diastolic blood pressure, and oxygen saturations. Two studies reported the occurrence of an adverse event (oxygen saturations, blood pressure and heart rate changes) but noted that changes were transient and not clinically significant. Overall, all studies concluded that MI-E was a safe intervention in this patient cohort. Conclusion Overall, the use of MI-E in the acutely intubated patient does not result in adverse events that are clinically significant. However, limitations to the evidence base should be acknowledged and include a lack of definition and variation in outcome measures used and small sample sizes across studies. Larger clinical trials are needed, to further evaluate the safety of MI-E on clinically important parameters that are more clearly defined.