Background: 5-aminolevulinic acid (5-ALA) enhances intraoperative high grade glioma (HGG) tissue visualization. Despite promising randomized clinical trial data suggesting survival benefit for 5-ALA-guided HGG surgery, patient outcome efficacy is not universally accepted. Methods: We performed a systematic review of the literature to evaluate whether there is a beneficial effect upon survival and extent of resection from the utilization of 5-ALA in HGG surgery. Literature regarding 5-ALA usage in HGG surgery was reviewed according to PRISMA guidelines. Results: 3,756 published studies were screened, 536 evaluated, and 45 included. Of studies that directly compared the use of 5-ALA to white light (28.9%), 5-ALA lead to a better progression-free survival (PFS) and overall survival (OS) in 88.4 and 67.5% of patients, respectively. 42.2% demonstrated that 5-ALA use was associated with less post-op neurological deficits, whereas 23.3% of studies showed that surgeries using 5-ALA lead to more deficits. 34.5% demonstrated no difference between 5-ALA and without. Conclusions: 5-ALA was found to be associated with a greater extent of resection and longer OS and PFS in HGG surgeries. Postop neurologic deficit rates were inconclusive when comparing 5-ALA groups to white light groups. 5-ALA is a useful surgical adjunct for HGG resection with preserved patient safety.