Objective. This study seeks to explore the efficacy and prognosis of stereotactic aspiration for malignant middle cerebral artery infarction (mMCAI). Methods. A total of 50 mMCAI patients who were diagnosed and treated in our hospital from January 2018 to June 2020 were collected and then randomly divided into control group (decompressive craniectomy, n = 24) and study group (stereotactic aspiration, n = 26). After 1 and 6 months of treatment, the scores of the National Institutes of Health Stroke Scale (NIHSS), Glasgow Coma Scale (GCS), Barthel Index, and modified Rankin Scale (mRS) were used to evaluate the therapeutic effect. Additionally, the mortality and survival rates after treatment were recorded to compare the prognostic effect between the two groups. Results. One month after treatment, the GCS scores and Barthel Index score increased in both the control and study groups and were significantly higher in the study group. The follow-up results at 1 and 6 months after treatment showed that in comparison with the control group, stereotactic aspiration led to a higher survival rate and lower mortality rate; the latter had superior NIHSS score and mRS score and better prognosis. Conclusion. In comparison with decompressive craniectomy, stereotactic aspiration shows outstanding clinical efficacy and more advantages in the treatment of mMCAI. Therefore, stereotactic aspiration is more worthy of clinical application.