The proposed systematic review will evaluate the evidence on the effectiveness and safety of enhanced post-operative care (EPC) units on patient and health service outcomes in adult patients following non-cardiac, non-neurological surgery. The increase in surgical procedures globally has placed a significant economic and societal burden on health care systems. Recognizing this challenge, EPC units have emerged as a model of care, bridging the gap between traditional, ward-level care and intensive care. EPC offers benefits such as higher staff-to-patient ratios, close patient monitoring (eg, invasive monitoring), and access to critical interventions (eg, vasopressor support). However, there is a lack of well-established guidelines and empirical evidence regarding the safety and effectiveness of EPC units for adult patients following surgery. This review will include studies involving adult patients (≥ 18 years) undergoing any elective or emergency non-cardiac, non-neurological surgery, who have been admitted to an EPC unit. Experimental, quasi-experimental, and observational study designs will be eligible. This review will follow the JBI methodology for systematic reviews of effectiveness. The search strategy will identify published and unpublished studies from the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), and Scopus, as well as gray literature sources, from 2010 to the present. Two independent reviewers will screen studies, extract data, and critically appraise selected studies using standardized JBI assessment tools. Where feasible, a statistical meta-analysis will be performed to combine study findings. The certainty of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. PROSPERO CRD42023455269.