Background: We recently reported a new approach, namely postconditioning with lactate-enriched blood (PCLeB), for cardioprotection in patients with ST-segment elevation myocardial infarction (STEMI). Objectives: We examined the effects of PCLeB on plasma NT-proBNP levels months after myocardial infarction (MI). Methods: The study included consecutive patients ( n = 31) undergoing percutaneous coronary intervention (PCI) for anterior STEMI within 12 h of symptom onset in our hospital between March 2014 and August 2018. We retrospectively compared plasma NT-proBNP levels several months after MI in these patients with those in historical control patients ( n = 32). The control patients included consecutive patients who underwent successful PCI without PCLeB for anterior STEMI within 12 h of symptom onset in our hospital between March 2009 and February 2014. We compared the highest plasma NT-proBNP values 6–10 months after MI in the postconditioned patients with the lowest plasma NT-proBNP values 6–10 months after MI in the control patients. In the PCLeB protocol, the duration of each brief reperfusion was increased stepwise from 10 to 60 s. Lactated Ringer’s solution (30 mL) was injected directly in the culprit coronary artery at the end of each brief reperfusion. Each ischemic episode lasted 60 s. Results: Plasma NT-proBNP levels in the postconditioned patients months after MI (211 ± 207 pg/mL) were significantly lower than those in the control patients (516 ± 598 pg/mL; p < 0.0001). Conclusion: PCLeB was associated with reduced plasma NT-proBNP levels months after MI.