Superior semicircular canal dehiscence (SSCD) is caused by bony defects in the osseous shell of the arcuate eminence separating the labyrinth and the intracranial space. This pathologic third window causes hydroacoustic transmission resulting in debilitating symptoms. We examine the pathophysiologic association between metabolic markers, previous medical history, and SSCD symptoms before and after middle fossa craniotomy (MFC) treatment. This study was conducted between March 2011 and September 2020 with patients with SSCD who underwent MFC. We used a Fisher test to compare variables, including bilateral SSCD, second surgery, ear anomaly, osteoporosis, arthritis, vitamin D, and preoperative/postoperative symptoms, and others. Point-biserial correlation analysis was performed to test correlations between continuous variables and categorical variables. A total of 250 patients with SSCD underwent MFC repair. There was significant postoperative resolution in all symptoms (P < 0.0001). Laboratory 25-hydroxyvitamin D values correlated with preoperative aural fullness (rpb= 0.29; P= 0.03), and preoperative disequilibrium (rpb= -0.32; P= 0.02). Serum calcium values correlated with preoperative hearing loss (rpb= 0.16; P= 0.02). Osteoporosis history (n= 16; 6%) was more prevalent in female patients (P= 0.0001), associated with higher levels of preoperative hearing loss (odds ratio, 4.56; P= 0.02) and higher postoperative hearing loss resolution (odds ratio, 2.89; P= 0.0509). Certain metabolic markers may predict SSCD presentation before and after surgery. Previous history of osteoporosis, autoimmune conditions, or arthritis may play a role in SSCD pathophysiology and can help predict clinical outcomes. Future evaluation should take metabolic laboratory values and acquire an exact medical history.