PURPOSE: Patients with syndromic craniosynostosis and midface hypoplasia often undergo midface advancement to improve respiratory function, orbital relationships, and facial appearance. This study compares the perioperative morbidity of a large cohort of subjects who underwent transcranial or subcranial midface distraction. METHODS: Demographic and perioperative data were compared between those who underwent transcranial or subcranial midface DO between July 1999 and December 2017. Univariate analysis was conducted using chi-square and Fisher exact tests for categorical variables, and Mann-Whitney U test for continuous variables. Multivariate analysis was conducted using logistic regression modeling. Complications were graded using the Clavien-Dindo classification. RESULTS: Sixty-four subjects (34 female, 30 male, age 8.5 ± 4.0yrs) underwent a total of 71 midface distraction procedures (26 transcranial, 45 subcranial, follow up 106 ± 52 days). There was a total of 28 (39%) complications. The transcranial cohort had a significantly higher frequency of complications (58%) compared to the subcranial cohort (29%, p=0.017), with a significantly greater proportion of infection-related complications in the transcranial cohort (80% vs 54%, p=0.028). Transcranial complications included cranial contamination, whereas most subcranial cohort infections were superficial or limited facial abscesses. The only significant predictor variable for complications in a multivariate analysis was whether the osteotomy approach was transcranial as opposed to subcranial, with an odds ratio of 5.44 (p=0.017). Transcranial procedures had significantly longer mean operating time (351 ± 66 minutes) compared to subcranial procedures (299 ± 80 minutes, p=0.003), and required significantly higher weight-adjusted volume of blood transfusion (81 ± 60 vs 57 ± 47 mL/kg, p=0.010). There was a trend towards the transcranial cohort having longer mean length of hospital stay (9 ± 9 vs 7 ± 6 days, p=0.071). CONCLUSION: Complication rates in midface distraction remain high, with transcranial procedures having significantly higher complication rates, infection-related complications, and severity of complications. Compared to subcranial midface distraction, transcranial procedures required significantly longer operating times and greater volume of weight-adjusted blood transfusion. While the goals of surgery often dictate choice of osteotomy, a thorough understanding of the risks associated with transcranial procedures must be understood by surgeon and patient alike.