Objective: In this study, we aimed to evaluate the effects of decompressive craniectomy (DC) on the brain death (BD) determination process in the pediatric intensive care unit (PICU). Materials and Methods: All children who were diagnosed with BD in the PICU between 2009 and 2020 were included in this study. Patient demographics, causative mechanisms, BD examinations, and ancillary tests used were recorded. The time intervals (from PICU admission to first BD examination, from first BD examination to BD diagnosis) and number of BD examinations were compared between patients with and without DC. Results: During the study period, 70 pediatric cases were diagnosed with BD among 513 total deaths (13.6%). Their median age was 54.5 months [interquartile range (IQR): 24-140]. Transcranial Doppler ultrasound (TCD) was performed in 66 patients (94.3%). The most common combination of ancillary tests was the apnea test and TCD combination, which was performed in 56 patients (80%). Thirty-four children (48.6%) experienced immediate surgery for DC. Patients with DC had a higher median number of BD examinations than patients without DC [3 (IQR: 2-3) vs. 2 (IQR: 1-2), P < .001]. The patients with DC had a longer time interval between the first examination and declaration of BD than patients without DC [45.5 hours (IQR: 21.7-91.7) versus 15 hours (IQR: 2-31.2), P < .006]. Conclusion: Decompressive craniectomy may complicate BD determination and cause challenges for brain death diagnosis based on cerebral flow imaging techniques. The lack of specific recommendations for this patient group in the guidelines causes a delayed diagnosis of BD. Cite this article as: Ekici B, Ersayoğlu İ, Yazıcı Özkaya P, et al. Impact of decompressive craniectomy on diagnosing brain death in children. Turk Arch Pediatr. 2024;59(1):93-97.