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Cranioplasty Timing After Decompressive Craniectomy: A Meta-Analysis of 4703 Patients. BACKGROUND AND OBJECTIVES: Cranioplasty (CP) is a critical neurosurgical intervention typically performed after decompressive craniectomy (DC). However, the optimal timing remains uncertain due to conflicting evidence and heterogeneous study designs. This pooled comparative meta-analysis aims to address this gap. METHODS: We conducted a systematic search for studies reporting outcomes of patients who underwent primary DC followed by CP on September 2024. Ultra-early CP was defined as ≤35 days, early CP as ≤86 days, and late CP as >86 days after DC. Outcomes included functional recovery measured by various scales and procedure-related complications. RESULTS: Thirty-eight studies (n = 4703) were included. Early CP was associated with improved functional outcomes: Karnofsky performance scale (mean difference [MD] 15.50, 95% CI [0.80, 31.80], P < .0001), Barthel Index (MD 13.10, 95% CI [0.24, 25.96], P = .01), functional independence measure (MD 11.23, 95% CI [7.61, 14.85], P < .00001), and activities of daily living (MD 13.65, 95% CI [1.44, 25.86], P = .03), compared with late CP. Other scales showed no significant differences. Overall complication rates did not differ between early and late CP (risk ratio 1.08, 95% CI [0.83, 1.41], P = .55), except for hydrocephalus, which was more common in early CP (risk ratio 1.58, 95% CI [1.07, 2.33], P = .02). No statistically significant differences in complication rates were observed for the ultra-early subgroup. CONCLUSION: Our findings suggest that early CP is associated with improved neurological function and greater daily independence, reflected by higher Karnofsky performance scale, Barthel Index, functional independence measure, and activities of daily living scores, without a significant increase in overall complication rates compared with late CP after DC. However, hydrocephalus appears more frequently after early CP. Standardized, multicenter prospective studies using consistent timing definitions are needed to refine individualized CP strategies.