OBJECTIVES To compare the safety and efficacy of del-Nido cardioplegia (DNC) with traditional 4:1 cold blood cardioplegia (CBC) in coronary artery bypass grafting and/or valve surgeries in elderly patients. METHODS The present study is a retrospective case-series study that included 302 consecutive patients aged 70 years and over who underwent on-pump valve surgery and/or CABG. DNC was administered to 90 patients and CBC to 212 patients. After propensity-score matching, 89 pairs were compared. The safety and efficacy were analysed between the two groups. RESULTS Compared with the CBC group (2185.8±582.9ml, P<0.001), the volume of infused cardioplegia was less in the DNC group (1423.6±259.5ml). The DNC group had a lower incidence of postoperative intra-aortic balloon pump (IABP) implantation (1.1% vs 9.0%, RR=0.791, P=0.034) and higher left ventricular ejection fraction (LVEF) at discharge (58.5±9.1% vs 55.7±8.6%, P=0.007). The estimated glomerular filtration rate (eGFR) in the DNC group was higher when the patient was transferred to the intensive care unit (78.2±25.1 ml/min/1.73m ² vs 69.7±20.2 ml/min/1.73m ², P=0.021), but no significant differences were identified after 24 hours. The serum lactate values of the DNC group were significantly lower than those of the CBC group (0hrs: 2.8±1.5 vs 3.6±2.0, P=0.001; 3hrs: 3.6±2.7 vs 4.9±2.6, P<0.001; 6hrs: 4.0±3.0 vs 6.1±3.3, P<0.001; 9hrs: 4.4±3.3 vs 5.9±3.6, P=0.004). There were no differences between the two groups in respect of lactate levels at 12 hours and thereafter. Postoperative creatinine kinase-MB concentrations were similar between the two groups. CONCLUSIONS Del-Nido cardioplegia is safe and effective in elderly patients undergoing CABG and/or valve surgery.