Decompressive hemicraniectomy (DHC) has proven efficacious for the treatment of malignant middle cerebral artery infarction (mMCAI) only in patients less than 60 years. This study aimed to assess the effectiveness of DHC in patients up to 80. This is a prospective, randomized, controlled trail comparing the outcomes with or without DHC in patients aged 18-80 with mMCAI (ChiCTR-TRC-11001757). The primary outcome measure was the modified Rankin Scale (mRS) scores at 6 months. The secondary outcome measures included the 6- and 12-month mortality and the mRS scores after 1 year. The prognosis of patients was evaluated independently by two blinded investigators. In addition, subgroup analyses were done for those above 60 years of age. All analyses were by intention-to-treat. A significant reduction in the poor outcome (mRS > 4) following DHC was reached after 36 patients had completed the follow-up period of 6 months. The trial was then terminated when 47 participants (24 in the surgical group vs. 23 in the medical group) had been recruited. The final analysis, based on the outcome data of the 47 patients, showed that DHC significantly reduced mortality at 6 and 12 months (12.5 vs. 60.9 %, P = 0.001 and 16.7 vs. 69.6 %, P < 0.001, respectively), and significantly fewer patients had a mRS score > 4 after surgery (33.3 vs. 82.6 %, P = 0.001 and 25.0 vs. 87.0 %, P < 0.001, respectively). Similar results were present in the subgroup analyses of elderly participants For patients up to 80 years who suffered mMCAI, DHC within 48 h of stroke onset not only is a life-saving treatment, but also increases the possibility of surviving without severe disability (mRS = 5).