Background: The effect of the ABCDEF bundle (Assess, prevent, and manage pain; Both spontaneous awakening and spontaneous breathing trials; Choice of analgesia and sedation; Delirium: assess, prevent, and manage; Early mobility and exercise; and Family engagement and empowerment) on patient outcomes such as delirium is potentially optimised when the bundle is implemented in its entirety. Objective: To systematically synthesise the evidence on the effectiveness of the ABCDEF bundle delivered in its entirety on delirium, function, and quality of life in adult intensive care unit patients. Design: Systematic review and meta-analysis. Data source: Electronic databases including MEDLINE, CINAHL, PsycINFO, Web of Science, Cochrane Library, Joanna Briggs Institute's Evidence Based Practice, Australian New Zealand Clinical Trials Registry, and Embase were searched from 2000 until December 2021. Review methods: Inclusion criteria included (1) adult intensive care unit patients (2) studies that described the ABCDE or ABCDEF bundle in its entirety (3) studies that evaluated delirium, functional outcomes, or quality of life. Studies were excluded if they investigated long-term intensive care unit rehabilitation patients. Two reviewers independently screened records and full text, extracted data, and undertook quality appraisals with discrepancies discussed until consensus was reached. Random effects meta-analyses were conducted for delirium but was not possible for other outcomes. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to assess the certainty of the synthesised findings of the body of evidence. The study protocol was registered on PROSPERO (CRD 42019126407). Results: A total of 18 studies (29,576 patients) were included in the descriptive synthesis. Meta-analysis of six studies (2000 patients) identified decreased delirium incidence following implementation of the ABCDEF bundle when compared with standard practice, (risk ratio = 0.57; CI, 0.36–0.90 p = 0.02) although heterogeneity was high (I2 = 92%). When compared with standard practice, a meta-analysis of five studies (3418 patients) showed the ABCDEF bundle statistically significantly reduced the duration of intensive care unit delirium (mean difference (days) – 1.37, 95% CI -2.61 to − 0.13 p = 0.03; I2 96%). Valid functional assessments were included in two studies, and quality of life assessment in one. Conclusions: Although the evidence on the effect of the ABCDEF bundle delivered in its entirety is limited, positive patient delirium outcomes have been shown in this meta-analysis. As this meta-analysis was based on only 4736 patients in eight studies, further evidence is required to support its use in the adult intensive care unit. Registration Details: PROSPERO (CRD 42019126407).