Aim: Multiple papers have reported the development of new-onset arthralgias with vedolizumab (VDZ) for the treatment of inflammatory bowel disease (IBD). Other studies have shown that VDZ may help in preexisting enteropathic spondyloarthropathy. We sought to probe this issue by conducting a systematic review. Methods: Embase, Medline, Cochrane Central, and Web of Science were searched up to June 29, 2020 for randomized controlled trials evaluating vedolizumab treatment in patients with IBD in which development of arthralgias was noted. Risk of bias and quality were assessed using Cochrane’s collaboration tool and the GRADE system, respectively. PROSPERO registration number: CRD42020197101. Results: Four hundred sixty-one discrete articles were retrieved. Five studies (n=2,899) met inclusion criteria. Comparing the risk of arthralgia in patients treated with VDZ and placebo yielded odds ratio’s which ranged between 1.01 (95% confidence interval (CI) 0.61-1.65) and 10.20 (95% CI: 0.53-195.78). While each study noted an increased incidence of arthralgias in patients receiving VDZ, none proved statistically significant. Studies were heterogeneous in disease populations, VDZ dosage, time-points for evaluation, and data points collected. Post-hoc analyses suggested an increased risk of arthralgias in patients with prior TNF inhibitor use. Conclusion: The included studies showed a trend toward increased arthralgias in patients with IBD who received VDZ. However, our study lacked any statistically significant findings to identify a clear link. More research is needed to substratify which patients develop arthralgias when treated with VDZ in order to better understand whether heightened risk can be predicted prior to treatment initiation.