Objective To investigate the prognosis of electrocardiogram (ECG) changes secondary to acute right and left large-scale middle cerebral artery (MCA) infarction, and to provide reference data for early clinical evaluation and intervention.Methods A total of 54 patients with acute large-scale MCA infarction who were admitted to our hospital from December 2014 to March 2016 were enrolled and divided into left MCA infarction group (n=20) and right MCA infarction group (n=34). National Institutes of Health Stroke Scale (NIHSS) score, Barthel index (BI), and modified Rankin score on admission and at 1, 3, and 6 months after onset were compared between the two groups.Results There was no significant difference in mortality within the first month between the two groups (χ²=1.975, P>0.05). The left MCA infarction group had a significantly lower BI score at 6 months after onset than the right MCA infarction group (t=-3.161, P<0.05). No matter whether there were secondary ECG changes, the left MCA infarction group had significantly higher NIHSS scores at 1, 3, and 6 months after onset than the right MCA infarction group (all P<0.05).Conclusions The prognosis may be different between patients with ECG changes secondary to right and left large-scale MCA infarction.