Background: The efficacy and safety of vedolizumab in bio-naïve patients with ulcerative colitis (UC) and Crohn's disease (CD) remain unknown. Aims: To perform a meta-analysis regarding vedolizumab as first line of biological therapy for UC or CD. Methods: A systematic review of Medline, EMBASE, and Cochrane databases per December 2020 was undertaken. Meta-analysis was conducted using random-effects models. Results: This systematic review identified 79 eligible studies with 4,520 and 3,494 bio-naïve patients with UC and CD, respectively, and 8,105 and 11,140 bio-exposed patients. Among bio-naïve patients with UC, a total of 40.0% (95%CI 27.0–54.0, I²=86%) and 63.9% (95%CI 47.0–79.2, I²=36%) achieved clinical remission at weeks 14 and 52, respectively. The corresponding rates in CD were 54.0% (95%CI 42.0–66.0, I²=23%), and 61.7% (95%CI 55.2–68.1, I²=0%). Bio-naïvety was associated with a higher probability of clinical remission at week 52 in UC (relative risk (RR)=1.32 (95%CI 1.14–1.53)), while this was only apparent until week 26 in CD (RR=1.60 (95%CI 1.30–1.95)). Finally, bio-naïve UC patients had a lower risk of serious adverse events (RR=0.29 (95%CI 0.09–0.95)). Conclusion: Vedolizumab was found to have a favorable efficacy and safety profile in bio-naïve patients with UC and CD. The findings have implications in the management of IBD.