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Background There is very few information regarding pain after craniotomy in children. Objectives This multicentre observational study assessed the incidence of pain after major craniotomy in children. Methods After IRB approval, 213 infants and children who were <10 years old and undergoing major craniotomy were consecutively enrolled in nine Italian hospitals. Pain intensity, analgesic therapy, and adverse effects were evaluated on the first 2 days after surgery. Moderate to severe pain was defined as a median FLACC or NRS score ≥4 points. Severe pain was defined as a median FLACC or NRS score ≥7 points. Results Data of 206 children were included in the analysis. The overall postoperative median FLACC/ NRS scores were 1 ( IQR 0 to 2). Twenty-one children (16%) presented moderate to severe pain in the recovery room and 14 (6%) during the first and second day after surgery. Twenty-six children (19%) had severe pain in the recovery room and 4 (2%) during the first and second day after surgery. Rectal codeine was the most common weak opioid used. Remifentanil and morphine were the strong opioids widely used in PICU and in general wards, respectively. Longer procedures were associated with moderate to severe pain ( OR 1.30; CI 1.07-1.57) or severe pain ( OR 1.41; 1.09-1.84; P < 0.05). There were no significant associations between complications, pain intensity, and analgesic therapy. Conclusion Children receiving multimodal analgesia experience little or no pain after major craniotomy. Longer surgical procedures correlate with an increased risk of having postoperative pain. [ABSTRACT FROM AUTHOR]