Background Strategies for cardio-protection are essential in coronary artery bypass graft surgery. The authors explored the relationship between cardioplegia volume, left ventricular mass index and ischemia time by means of the infused cardioplegia index and its relationship with post-operative low cardiac output syndrome. Design All patients undergoing coronary artery bypass graft surgery between January 2013 and December 2015 were included. Low cardiac output syndrome was defined according to criteria of the SEMICYUC's consensus document. The perioperative factors associated with low cardiac output syndrome were estimated, and using a ROC curve, the optimum cut-off point for the infused cardioplegia index to predict the absence of low cardiac output syndrome was calculated. Results Of 360 patients included, 116 (32%) developed low cardiac output syndrome. The independent risk predictors were: New York Heart Association Functional Classification (OR 1.8 [95% CI = 1.18–2.55]), left ventricle ejection fraction (OR 0.95 (95% CI = 0.93–0.98]), ICI (OR 0.99 [95% CI = 0.991–0.996]) and retrograde cardioplegia (OR 1.2 [95% CI = 1.03–1.50]). The infused cardioplegia index showed an area under the ROC curve of 0.77 (0.70–0.83; p Conclusions The infused cardioplegia index presents an inverse relationship with the development of post-operative low cardiac output syndrome. This index could form part of new strategies aimed at optimizing cardio-protection. The total volume of intermittent cardioplegia, especially that of maintenance, should probably be individualized, adjusting for ischemia time and left ventricle mass index.