Remote ischemic conditioning (RIC) is used to protect against myocardial injury. However, there is no adequate evidence for comprehensive RIC in elderly patients with ST-segment elevation myocardial infarction (STEMI). This study aimed to test whether comprehensive RIC, started pre-primary percutaneous coronary intervention (PPCI) and repeated daily on 1-30 days post-PPCI, can improve myocardial salvage index (SI), left ventricular ejection fraction (LVEF), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and 6-min walk test distance (6MWD) in elderly patients with acute STEMI during 12 months follow-up.328 consenting elderly patients were randomized to receive standard PPCI plus comprehensive RIC (the treatment group) or standard PPCI (the control group). SI at 5-7 days after PPCI, LVEF, left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), KCCQ-CSS, 6MWD and adverse events rates were measured and assessed.SI was significantly higher in the treatment group [interquartile range (IQR): 0.38-0.66, P = 0.037]. There were no significant differences in major adverse events at 12 months. Although the differences of LVEDVI, LVESVI and LVEF between the treatment group and the control group did not reach statistical significance at 6 months and 12 months, LVEF tended to be higher, LVEDVI tended to be lower in the treatment group. The KCCQ-CSS was significantly higher in the treatment group at 1 month (IQR: 46.5-87, P = 0.001) and 12 months (IQR: 55-93, P = 0.008). There was significant difference in 6MWD between the treatment group and the control group (IQR: 258-360 vs. IQR: 250-345, P = 0.002) at 1 month and (IQR: 360-445 vs. IQR: 345-432, P = 0.035) at 12 months. A modest correlation was found between SI and LVEF (r = 0.452, P < 0.01), KCCQ-CSS ( r = 0.440, P < 0.01) and 6MWD ( r = 0.384, P < 0.01) respectively at 12 months.The comprehensive RIC can improve SI, KCCQ-CSS and 6MWD. It may be an adjunctive therapy to PPCI in elderly patients with STEMI.© 2022 JGC All rights reserved; www.jgc301.com.