BACKGROUND: Scalp block is regional anesthetic injection along nerves innervating the cranium. Scalp blocks for craniotomy may decrease postoperative pain and opioid consumption. Benefits may extend beyond the anesthetic period. OBJECTIVE:To analyze evidence for scalp block on postoperative pain and opioid use. METHODS: This systematic review and meta-analysis, Prospective Register of Systematic Reviews registration (CRD42022308048), included Ovid Medical Literature Analysis and Retrieval System Online, Embase, and Cochrane Central Register of Controlled Trials inception through February 9, 2022. Only randomized controlled trials were included. We excluded studies not reporting either main outcome. Duplicate reviewers performed study selection, risk of bias assessment, data extraction, and evidence certainty Grading of Recommendations Assessment, Development, and Evaluation appraisal. Main outcomes were postoperative pain by visual analog scale within 72 hours and opioid consumption as morphine milligram equivalent (MME) within 48 hours. RESULTS: Screening filtered 955 studies to 23 trials containing 1532 patients. Risk of bias was overall low. Scalp block reduced postoperative pain at 2 through 72 hours, visual analog scale mean differences of 0.79 to 1.40. Opioid requirements were reduced at 24 hours by 16.52 MME and 48 hours by 15.63 MME. CONCLUSION: Scalp block reduces postoperative pain at 2 through 48 hours and may reduce pain at 72 hours. Scalp block likely reduces opioid consumption within 24 hours and may reduce opioid consumption to 48 hours. The clinical utility of these differences should be interpreted within the context of modest absolute reductions, overall care optimization, and patient populations. This is the first level 1A evidence to evaluate scalp block efficacy in craniotomy.