Endonasal endoscopic skull base surgery (EESBS) often requires significant alterations in intranasal anatomy. For example, posterior septectomy (PS) with middle turbinate resection (MTR) is frequently performed to provide access to large sellar and clival tumors. However, little is known about the alterations that occur in sinonasal physiology. This study was designed to assess changes in sinonasal physiology after virtually performed endoscopic skull base surgery. Three-dimensional models of the sinonasal passage were created from computed tomography scans in three subjects with varying anatomy: no SD (SD), right anterior SD, and left anterior SD, respectively. Four additional surgery types were performed virtually on each model: endoscopic transsphenoidal approach (ETSA) with small (1 cm) PS (smPS), ETSA with complete (2 cm) PS, ETSA with smPS and right MTR, and ETSA with complete PS and right MTR. Computational fluid dynamics (CFD) simulations were performed on the 3 presurgery and 12 virtual surgery models to assess changes from surgery types. Increased nasal airflow corresponded to amount of tissue removed. Effects of MTR on unilateral airflow allocation were unchanged in subject with no SD, worsened in leftward SD, and reversed in rightward SD. Severity of airflow and mucosal wall interactions trended with amount of tissue removed. MTR hindered flow interactions with the olfactory mucosa in subjects with SD. CFD simulations on virtual surgery models are able to reasonably detect changes in airflow patterns in the computer-generated nasal models. In addition, each patient's unique anatomy influences the magnitude and direction of these changes after virtual EESBS. Once future studies can reliably correlate CFD parameters with patient symptoms, CFD will be a useful clinical tool in surgical planning and maximizing patient outcomes.