Aim <p>Complications such as seizures, hydrocephalus, infection, and sinking skin flap may develop after decompressive craniectomy (DC). Sinking skin flap (SSF) and syndrome of the trephined (SoT) are recognized complications following DC. SoT is characterized by neurological symptoms, including motor deficits, headache, confusion, speech disturbance, lethargy, cognitive impairment, and dizziness, which may worsen with standing or Valsalva maneuvers and typically improve after cranioplasty. The aim of this study was to evaluate whether SSF is consistently associated with SoT and to identify factors predicting their development.</p> Materials and Methods <p>Among 138 patients who underwent decompressive craniectomy followed by cranioplasty, SSF was detected in 50 patients prior to cranioplasty. Patients who developed SoT were retrospectively analyzed.</p> Results <p>Comorbidity (p = 0.001), greater midline shift (p &lt; 0.001), and a decompressive craniectomy defect size &gt;100 cm² (p &lt; 0.001) were significantly associated with SSF. The incidence of SoT was 68% in the SSF (+) group compared to 28.4% in the SSF (–) group (p &lt; 0.001). Importantly, SoT was also observed in patients without SSF. A total recovery rate of 64.7% was observed in SoT patients overall; however, in the SSF (–) group with SoT (+), the recovery rate was 12%. Midline shift and Glasgow Outcome Scale (GOS) scores were significant in patients with SoT compared to those without SoT (p &lt; 0.001) .</p> Conclusion <p>SoT does not develop in all patients with SSF and may also occur in patients without SSF. Comorbidity, larger craniectomy defect size (&gt;100 cm²), increased midline shift, and lower GOS scores are important associated factors. These findings suggest that SSF is not a prerequisite for SoT, and clinical evaluation should be emphasized during postoperative follow-up.</p>