Objective: The outcome of decompressive craniectomy (DC) for severe traumatic brain injury (sTBI) patients with fixed dilated pupils (FDPs) is not clear. The objective of this study was to validate the outcome of DC in sTBI patients with FDPs. Patients: We retrospectively collected data from 207 sTBI patients with FDPs during the time period of May 4, 2003-October 22, 2013: DC group (n=166) and conservative care (CC) group (n=41). Measurements: Outcomes that were used as indicators in this study were mortality and favorable outcome. The analysis was based on the Glasgow Outcome Scale recorded at 6 months after trauma. Results: A total of 49.28% patients died (39.76% [DC group] vs 87.80% [CC group]). The mean increased intracranial pressure values after admission before operation were 36.20 +/- 7.55 mmHg in the DC group and 35.59 +/- 8.18 mmHg in the CC group. After performing DC, the mean ICP value was 14.38 +/- 2.60 mmHg. Approximately, 34.34% sTBI patients with FDPs in the DC group gained favorable scores and none of the patients in the CC group gained favorable scores. Conclusion: We found that DC plays a therapeutic role in sTBI patients with FDPs, and it is particularly important to reduce intracranial pressure as soon as possible after trauma. For the patients undergoing DC, favorable outcome and low mortality could be achieved.