Background: Some 19 million people are living with long-term conditions (LTC) in the UK. The growing burden of multiple LTC (the co-existence of ?2 LTC within an individual) is associated with reduced functional capacity and quality of life (QoL), increased healthcare utilisation, cost, and all-cause mortality.

Aim: To identify and summarise systematic review evidence of the benefits of exercise-based interventions across a comprehensive list of LTC.

Methods: Database searches were conducted in June 2022. Eligibility criteria included peer-reviewed systematic reviews of exercise-based interventions compared to usual care, no-exercise control or interventions that did not contain structured exercise, in adults diagnosed with an LTC. Outcomes included mortality, hospitalisation, exercise capacity, frailty, disability, physical activity and health-related QoL. Evidence was summarised by narrative synthesis.

Results: Electronic database searches yielded 11,074 unique records. 617 eligible systematic reviews were identified. One 'best' review was selected per LTC for further extraction and synthesis based on recentness, comprehensiveness, focus, methodology and outcomes. Preliminary results identified 25 LTC with strong evidence that exercise is beneficial. The benefits of exercise were unclear or conflicting for 13 LTC. No evidence was identified for 6 LTC.

Conclusion: LTC identified with clear indications for exercise-based interventions will inform the population for inclusion in the NIHR funded Personalised Exercise Rehabilitation FOR people with Multiple LTC (PERFORM) research programme; aiming to develop and evaluate a rehabilitation intervention for people living with multiple LTC.