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Abstract Background Resistance training is commonly recommended as part of secondary prevention for post-coronary artery bypass graft (CABG) patients in conjunction with aerobic exercise. Despite its potential benefits, there is currently a lack of studies investigating the impact of resistance training on proprotein convertase subtilisin kexin 9 (PCSK9). Aim To evaluate the effect of intensive resistance training on proprotein convertase subtilisin kexin 9 (PCSK9) levels among post-CABG patients undergoing cardiac rehabilitation (CR). Methods In this prospective, open-label, randomized trial, 87 post-coronary artery bypass graft (CABG) patients were randomly assigned into two groups: moderate to high intensity resistance training and aerobic training (n = 44) or aerobic training alone (n = 43) for a total of 12 sessions. Changes in PCSK9 levels was determined as a primary endpoint, while secondary endpoints included changes in the six-minute walk test (6-MWT) results, aerobic capacity, WHO-5 well-being index, fasting blood glucose, and lipid profile. Both groups underwent intention-to-treat analysis. Results Following completion of cardiac rehabilitation program, the intervention group demonstrated a significant decrease in mean PCSK9 levels when compared to the control group (β = -55 ng/ml, 95% CI -6.7 to -103.3, p = 0.026), as well as significant improvements in the 6-MWT result (β = 28.2 m, 95% CI 2.4–53.9, p = 0.033), aerobic capacity (β = 0.9 Mets, 95% CI 0.1–1.7, p = 0.021), and WHO-5 well-being index (β = 8.1, 95% CI 2.0–14.4, p = 0.011) in patients who received resistance and aerobic training. No statistically significant changes were observed in fasting blood glucose, cholesterol, LDL-C, HDL-C, and triglyceride levels. Conclusion Resistance training in CR significantly reduced PCSK­9 levels and increases patient’s functional capacity and quality of life. (NCT02674659 04/02/2016).