There are substantial gaps in our understanding of the influence of the endoscopic endonasal approach (EEA) for endoscopic skull base surgery on sinonasal-specific quality of life (QOL) as well as the instruments available for assessment. Our primary objective in this study was to characterize postoperative changes in sinonasal QOL, specifically using the 22-item Sino-Nasal Outcome Test (SNOT-22), with a secondary objective of delineating weaknesses in our current understanding of patient symptomatology after EEA for skull base surgery. A comprehensive literature review was conducted using PubMed, CINAHL, Cochrane Library, and SCOPUS for studies reporting SNOT-22 data pre- and postoperatively in patients who underwent EEA for skull base pathologies. Studies were limited to patients ≥18 years of age and excluded patients diagnosed with chronic rhinosinusitis (CRS). Nineteen unique studies with 27 separate data sets and a total of 1025 patients were used in this meta-analysis. Overall SNOT-22 scores statistically improved at the 6-month (p = 0.0009) and 1-year (p = 0.002) time-points. Patients with preoperative SNOT-22 scores ≥20 achieved postoperative improvements at 12-week (p < 0.00001), 6-month (p < 0.0001), 1-year (p < 0.00001), and long-term follow-up (p < 0.0001). Patients with preoperative SNOT-22 scores <20 remained stable and did not worsen postoperatively. Patients undergoing EEA for skull base pathologies who have impaired sinonasal QOL preoperatively demonstrated significant postoperative QOL improvements. Those patients with relatively normal preoperative sinonasal QOL remained asymptomatic postoperatively. This study supports the need for development of a contemporary disease- and approach-specific, validated QOL instrument for skull base pathologies.