Background: Although surgery is the mainstay of treatment for most pituitary adenomas, post-operative radiotherapy has been shown to be of benefit in improving tumor control and recurrence-free survival. To understand potential side effects of radiotherapy we performed a systematic review and meta-analysis to determine the efficacy and safety of post-operative radiotherapy for pituitary adenoma. Methods: A systematic review was performed according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. We searched PubMed, MEDLINE and Cochrane databases with no language or publication date restrictions. Outcomes included 5- and 10-year progression-free survival and adverse events rates. Results: A total of 48 studies from 1986-2016 met the inclusion criteria, with 7551 cumulative patients. The cumulative 5- and 10-year s progression-free survival rates were 90.8% (95% CI 86-94%) and 88.6% (95% CI 81-93%), respectively. The overall adverse events rate was 8% (95% CI 5-12%). All outcomes were associated with significant heterogeneity (I2 ≥ 70%). No differences in survival rates or adverse events in relation to study date, tumor pathology, radiosurgery system used or dose of radiation. Conclusions: Post-operative radiotherapy for pituitary adenomas is effective and safe. Because of the significant heterogeneity and lack of matched controls in the literature, optimum timing and dosage are still unclear. Further prospective studies are needed.