Introduction Autologous bone is a commonly used material for cranioplasty following decompressive craniectomy; however, it is accompanied by the inherent risk of resorption. This study aimed to identify factors associated with bone flap resorption (BFR) in patients undergoing autologous cranioplasty after decompressive craniectomy for traumatic brain injury. Methods A matched case-control study was conducted at Viet Duc University Hospital between January 2022 and July 2025. Cases were defined as patients who developed severe BFR requiring revision surgery. Each case was matched with two controls without BFR based on cranioplasty date and follow-up duration. The association of demographic, general health, trauma historyand peri-cranioplasty characteristics with BFR was assessed using conditional logistic regression. Results A total of 71 cases and 142 matched controls were included. BFR that required surgical revision occurred predominantly within two years after cranioplasty (90%). The mean time interval from cranioplasty to complication diagnosis was 444 ± 212 days. Large-sized bone flap (OR: 3.96, 95% CI: 1.86 - 8.43), fragmented bone flap (OR: 7.84, 95% CI: 1.38 - 44.53), and chronic viral hepatitis (either B or C) (OR: 4.32, 95% CI: 1.54 - 12.15) were independent associated factors of BFR. Young age (<18), frontal sinus fracture and ventriculoperitoneal shunt implantation showed a trend to increase risk of BFR but failed to reach statistical significance in multivariate analysis. Conclusions In our study, bone fragmentation, large bone flap size, and chronic viral hepatitis were associated with increased risk of bone flap resorption after autologous cranioplasty in TBI patients. Further studies are necessary to confirm these findings, especially the role of chronic viral hepatitis.