Fronto-orbital retrusion may occur after primary surgical correction of craniosynostosis, particularly in patients with syndromic craniosynostosis. This study investigated reoperation rates and factors contributing to FO relapse among this cohort. A retrospective review evaluated reoperation for FO relapse in patients with syndromic multisuture craniosynostosis who underwent primary fronto-orbital advancement (FOA) + calvarial vault remodeling (CVR) at our institution between 2004 and 2024. Revision surgeries included repeat FOA or monobloc advancement/distraction. FOA advancement distance was measured using postoperative computed tomography and Mimics software. ROC analysis evaluated the accuracy of FOA distance in predicting subsequent FO relapse. Conditional margins identified optimal advancement distances. Logistic regression of predictors of FO relapse adjusted for age at surgery, craniofacial syndrome, posterior vault distraction osteogenesis (PVDO), advancement distance, and postoperative helmet therapy. Fifty-two patients underwent a mean of 2.8±1.9 skeletal craniofacial procedures each. With a mean follow-up time of 9.2±6.5 years, 16 (30.8%) patients required reoperation for FO relapse. Larger advancement distances were the sole significant predictor of relapse, increasing the odds by 49.6% (OR 1.496, 95% CI: 1.085–2.063; P=0.014). Relapse rates were lower with advancements ≤17.2 mm (0.0%) than with further advancements (42.0%, P=0.002). Specifically, advancements >18.8 mm were associated with significantly higher relapse rates (P<0.05). Almost one-third of patients with multisuture syndromic craniosynostosis underwent FO region readvancement. Advancements <17.2 mm during initial FOA appeared to mitigate relapse, while advancing beyond 18.8 mm may increase the risk. Investigation of additional protective factors against FO relapse is encouraged to minimize surgical burden.