Abstract Introduction Frailty is common in patients with long-term cardiac conditions and is associated with poor clinical outcomes, but limited treatment options are available. Previous studies investigating interventions for frailty have shown positive results with physical activity interventions, however, these studies were largely based on general elderly populations. Aim To assess the impact of physical activity-based interventions on frailty and clinical outcomes in frail patients with long-term cardiac conditions. Methods A systematic review and meta-analysis was conducted based on the PRISMA guideline, using Medline, Embase, CENTRAL, PEDro, CINAHL electronic databases for articles published between 2000 and 2023. Studies which recruited adults >18 years with long-term cardiac conditions (including angina, acute coronary syndrome (ACS), valve disease, heart failure (HF), atrial fibrillation, cardiac surgery and congenital heart disease) who underwent physical activity-based interventions were included. The primary outcome was change in frailty (measured using a validated tool) post intervention. We also assessed the effect of interventions on mortality and hospitalisation. Results We screened 2697 records and reviewed 91 full-text articles; 12 studies (14 articles) were included, involving 1394 patients. Median age of participants ranged from 64 to 82 years. Five studies recruited participants with HF, 3 evaluated participants post transaortic valve implantation, 3 recruited cardiac surgical patients and 1 study evaluated participants post ACS. Physical activity-based interventions were multi-domain, including a mixture of aerobic, strength, balance, endurance and respiratory muscle training; the majority (N=10) had individualised exercise prescription. Meta-analysis of 8 randomised controlled trials (RCTs) showed statistically significant improvement in frailty associated with physical activity-based interventions compared to controls [pooled standardised mean difference (95% CI) = -0.34 (-0.59 to -0.08), p = 0.01, I2 = 48%]. Seven RCTs evaluated change in frailty by short physical performance battery (SPPB). Meta-analysis of these studies showed a statistically significant improvement in SPPB associated with physical activity-based interventions compared to controls [pooled mean difference (95% CI) = 0.83 (0.31-1.34), p = 0.002, I2 = 49%]. (Figure) The magnitude of improvement in SPPB exceeded the minimally clinically significant improvement of 0.5. Three studies evaluated the effect of physical activity-based intervention on clinical outcomes, all of which showed neutral effect on mortality and hospitalisation. Conclusion Physical activity-based interventions in patients with frailty and long-term cardiac conditions were associated with significant improvement in frailty status, with neutral effect on mortality and hospitalisation. Figure: Meta-analysis of 7 RCTs assessing effect of physical activity-based interventions on SPPB