While peanut oral immunotherapy (poit) represents a promising treatment for peanut allergies in children, safety concerns remain a common barrier to widespread adoption. We aimed to systematically assess available evidence to determine the risk and frequency of adverse events occurring during POIT, and examine study-level characteristics associated with their occurrence and severity. A systematic search of MEDLINE, EMBASE, and Web of Science was conducted through April 2019. Controlled and non-controlled studies evaluating POIT were eligible. Twenty-seven studies, involving 1488 subjects, were included. Adverse events to POIT were common and led to treatment discontinuation in 6.6% of children (95% CI 4.4-9.0; 27 studies, I 2 = 48.7%). Adverse events requiring treatment with epinephrine occurred among 7.6% (4.5-11.4; 26 studies, I 2 = 75.5%) of participants, at a rate of 2.0 per 10,000 doses (0.8-3.7; 15 studies, I 2 = 64.4). Use of a rush treatment phase and targeting a higher maintenance dose were associated with a higher risk and frequency of epinephrine use, while using co-treatments in addition to poit was associated with a lower risk of treatment discontinuation due to adverse events. While adverse events to POIT are common, this study provides promising explorative evidence that certain modifications to existing treatment protocols could significantly improve treatment outcomes.Peanut allergy is the leading cause of food-related allergic reactions for children in Western countries, affecting 1-3% of children 1-5 . While a small percentage of children grow out of their peanut allergy, the only currently recognised and supported treatment approach is allergen-avoidance and use of rescue medications for managing allergic reactions 6 . Avoidance, however, can be difficult because peanuts are widely present in many foods, and there is also the risk of contamination during manufacturing processes. In addition, labelling can be inadequate or misinterpreted by families and caregivers 7 . As such, accidental ingestion leading to reactions are common even under supposedly strict avoidance 8-10 , representing a significant burden on children and their families 11 .As such, there has been significant interest in developing approaches towards the prevention and treatment of peanut allergies. Oral immunotherapy (OIT) has recently emerged as an effective treatment in desensitising children with a variety of food allergies. While recent systematic reviews have demonstrated the effectiveness of POIT in achieving the immunological goal of desensitisation to peanut allergy, they have raised significant concerns regarding potential risks associated with treatment 12,13 . This has led to caution regarding the adoption of POIT in clinical practice outside of the trial setting. These previous reviews, however, were restricted to randomised controlled trials, omitting a large body of evidence from non-controlled studies that can provide greater evidence surrounding likely real-world outcomes associated with POIT in children. In l...