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Background: Pneumocephalus may be responsible for post-craniotomy headache but is easily overlooked in the clinical situation. In the present study, the relationship between the amount of intracranial air and post-craniotomy headache was investigated., Methods: A retrospective observational study was performed on 79 patients who underwent minimal invasive craniotomy for unruptured cerebral aneurysms. Those who had undergone previous neurosurgery, neurological deficit before and after surgery were excluded The amount of air in the cranial cavity was measured using brain computed tomography (CT) taken within 6 h after surgery. To measure the degree of pain due to intracranial air, daily and total analgesic administration amount were used as a pain index. Correlation between intracranial air volume and total consumption of analgesic during hospitalization was tested using Spearman rank correlation coefficients. Receiver operating characteristics (ROC) analysis was used to determine the amount of air associated with increased analgesic consumption over 72 h postoperatively., Results: The mean amount of intracranial air was 15.6 ± 9.1 mL. Total administration of parenteral and oral analgesics frequency were 6.5 ± 4.5, 13.2 ± 7.9 respectively. A statically significant correlation was observed between daily and total parenteral analgesic consumption after surgery and the amount of intracranial air at followed-up brain CT postoperatively within 24 h (r = 0.69, p < 0.001), within 48 h (r = 0.68, p < 0.001), and total duration after surgery (r = 0.84, p < 0.001). The optimal cut-off value of 12.14 mL of intracranial air predicts the use of parenteral analgesics over 72 h after surgery., Conclusions: Pneumocephalus may be a causative factor for post-craniotomy pain and headache with surgical injuries., (© 2022. The Author(s).)