Mechanical insufflation-exsufflation (MI-E) is traditionally used in the neuromuscular population. There is growing interest of MI-E use in invasively ventilated critically ill adults. We aimed to map current evidence on MI-E use in invasively ventilated critically ill adults. Two authors independently searched electronic databases MEDLINE, Embase, and CINAHL via the Ovid platform; PROSPERO; Cochrane Library; ISI Web of Science; and International Clinical Trials Registry Platform between January 1990–April 2021. Inclusion criteria were (1) adult critically ill invasively ventilated subjects, (2) use of MI-E, (3) study design with original data, and (4) published from 1990 onward. Data were extracted by 2 authors independently using a bespoke extraction form. We used Mixed Methods Appraisal Tool to appraise risk of bias. Theoretical Domains Framework was used to interpret qualitative data. Of 3,090 citations identified, 28 citations were taken forward for data extraction. Main indications for MI-E use during invasive ventilation were presence of secretions and mucus plugging (13/28, 46%). Perceived contraindications related to use of high levels of positive pressure (18/28, 68%). Protocolized MI-E settings with a pressure of ±40 cm H2O were most commonly used, with detail on timing, flow, and frequency of prescription infrequently reported. Various outcomes were re-intubation rate, wet sputum weight, and pulmonary mechanics. Only 3 studies reported the occurrence of adverse events. From qualitative data, the main barrier to MI-E use in this subject group was lack of knowledge and skills. We concluded that there is little consistency in how MI-E is used and reported, and therefore, recommendations about best practices are not possible.