It is recognized that stereotactic anatomical localization (SAL) is a useful tool in endoscopic sinus surgery (ESS), but it may be most beneficial for complex rather than routine sinus procedures. This review sought to determine the safety and efficacy of SAL in complex indications for ESS. PubMed, EMBASE, Centre for Reviews and Dissemination, and the Cochrane Library were searched from inception up to April 4, 2014. English studies comparing ESS with and without SAL in complex cases were included. Complex surgery included revision surgery, inverted papilloma, extensive sinus disease, or biopsy of tumors that are not exophytic. Safety outcomes included total, major, minor, orbital, dural, and major hemorrhage complications. Efficacy outcomes included operation completion, revision surgery, and patient-reported outcomes. Meta-analysis generated fixed-effects Mantel-Haenszel odds ratios (OR) and confidence intervals (CI). A total of 2,381 studies were identified, of which nine met the inclusion criteria. Meta-analyses indicated a reduction in the likelihood of total (OR = 0.58; 95% CI, 0.37-0.92), major (OR = 0.36; 95% CI, 0.18-0.75), and orbital complications (OR = 0.38; 95% CI, 0.17-0.83). There was no demonstrated benefit of SAL at reducing revision surgery (OR = 0.64; 95% CI, 0.38-1.08), major hemorrhage (OR = 0.77; 95% CI, 0.29-2.06), or minor complications (OR = 0.85; 95% CI, 0.48-1.50). Due to the rare outcomes under investigation, the included primary studies largely lacked the power to identify a statistically meaningful effect of SAL in ESS. However, meta-analyses of primary studies demonstrated a decreased likelihood of total, major, and orbital complications in complex ESS with the use of SAL.