Objective To investigate the short and long term prognostic effects of staging and single percutaneous coronary intervention (PCI) in high-risk non-ST elevation acute coronary syndromes (NSTACS) with multiple vessel lesions (MVD). Methods Clinical data of 80 high-risk NSTACS patients with MVD were retrospectively collected from January 2022 to September 2023. According to different treatment methods, the patients were divided into stage group (stage PCI, 40 cases) and disposable group (PCI, 40 cases). Staging group was treated by staging PCI. PCI was performed once in disposable group. The cardiac function indexes (left ventricular end-diastolic diameter (LVDD), left ventricular end-systolic diameter (LVED), N-terminal B-type natriuretic peptide (NT-proBNP)), perioperative related indexes, complications and major adverse cardiovascular events (MACE) of the two groups were analyzed and compared. Results At 4 weeks after surgery, LVDD, LVED and NT-proBNP in the two groups were significantly lower than before surgery, and LVDD, LVED and NT-proBNP in disposable group were significantly lower than those in stage group (P < 0.05). The per capita stent, the number of diseased vessels, the amount of contrast agent, PCI time, hospital stay and cost in the disposable group were significantly lower than those in the stage group (P < 0.05). There was no significant difference in the incidence of complications between the two groups (P > 0.05). The incidence of MACE in disposable group was significantly lower than that in stage group (P < 0.05). Conclusion Compared with staging PCI, single-PCI treatment of high-risk NSTACS with MVD can improve the cardiac function of patients, reduce the number of stents implanted, reduce the amount of contrast agent and economic expenditure, shorten the length of hospital stay, and reduce the incidence of MACE.