The beneficial effects of therapeutic hypothermia (TH) after decompressive craniectomy (DC) for malignant middle cerebral artery (MCA) infarction are controversial. We conducted a systematic review and meta-analysis to assess the clinical efficacy of TH in aforementioned patients. A systematic literature search was conducted to find articles published up to April 2019 evaluating the effect of combining TH and DC on short-term (≤30 days) and long-term (>6 months) mortality and neurological outcomes in patients with malignant MCA infarction. Pooled relative risk (RRs) with 95% confidence interval (CI) were calculated using the Mantel-Haenszel fixed-effects model or the DerSimonian-Laird random-effects. Patient data was analyzed for a total of 289 patients from four selected studies and two abstracts. Compared to DC alone, combining DC and TH had a tendency to reduce short-term mortality (RR = 0.52, 95% CI 0.26 to 1.05, P = 0.07, I2 = 0%) but had no significant effects on long-term mortality (RR = 1.26, 95% CI 0.58 to 2.76, P = 0.56, I2 = 68%) or neurological outcomes (RR = 0.81, 95% CI 0.53 to 1.24, P = 0.34, I2 = 30%). Using TH in tandem with DC did not show definite short- or long-term survival benefits in our study, but may tend to reduce the short-term mortality of patients with malignant MCA infarction. Copyright © 2019 Elsevier B.V. All rights reserved.