Objective To explore the application effect of the "Zero-Defect" nursing management concept in the perioperative period of interventional therapy for acute cerebral infarction (ACI). Methods A randomized controlled trial design was adopted, eighty ACI patients who had scheduled for interventional therapy were selected as the study subjects, and they were divided into a control group or an observation group using a random number table, with 40 patients in each group. The control group received routine nursing management, based on which the observation group received nursing care guided by the "Zero-Defect" nursing management concept. Neurological function (National Institutes of Health Stroke Scale [NIHSS]) and quality of life (36-item Short Form Health Survey [SF-36]) before the intervention and at 3 months of follow-up, the overall incidence of complications during hospitalization (including cerebral hemorrhage, puncture site hematoma, and intracranial infection), and nursing satisfaction were compared between the two groups. Results Before the intervention, there was no statistically significant difference in the NIHSS score or the SF-36 score between the two groups (all P>0.05). At 3 months of follow-up, NIHSS scores decreased and SF-36 scores increased in both groups compared to baseline; furthermore, the NIHSS score in the observation group was lower than that in the control group, and the SF-36 score was higher than that in the control group (all P<0.05); the overall incidence of complications during hospitalization (including cerebral hemorrhage, puncture site hematoma, and intracranial infection) was lower in the observation group than in the control group (P<0.05), and the overall nursing satisfaction was higher in the observation group than in the control group (P<0.05). Conclusion The application of the "Zero-Defect" nursing management concept in the perioperative care of interventional therapy for ACI can effectively promote the recovery of patients' neurological function, improve quality of life, reduce the incidence of complications, and enhance patients' satisfaction with nursing care.