Objective: While infliximab combined to thiopurines is more effective than infliximab monotherapy in patients with Crohn's disease (CD) and ulcerative colitis (UC), the impact of adding thiopurines to vedolizumab remains controversial. We emulated two target trials comparing the effectiveness of combination therapy versus vedolizumab monotherapy in CD and UC. Design: Based on two U.S. and the French nationwide healthcare databases, patients with CD and UC who initiated vedolizumab were identified. The study methodology, including confounding adjustment and outcome definitions, were previously validated in successful emulations of the SONIC and SUCCESS trials. Risk ratios for treatment failure based on hospitalisation or surgery related to disease activity, treatment switch, or prolonged corticosteroids use, were estimated after 1:1 propensity score (PS) matching. Results: Among a total of 10,299 vedolizumab users, 804 CD and 1,088 UC pairs of combination therapy versus vedolizumab monotherapy users were PS-matched. Treatment failure occurred at week 26 in 236 (29.3%) and 376 (34.3%) CD patients and at week 16 in 236 (21.7%) and 263 (24.2%) UC patients initiating combination therapy and vedolizumab monotherapy, respectively. The risk of treatment failure was decreased with combination therapy compared to vedolizumab monotherapy in CD (RR 0.85, 95%CI 0.74 to 0.98), and to a lesser extent in UC (RR 0.90, 0.77 to 1.05). Findings were consistent across databases. Conclusion: Using validated methodologies, combination therapy with vedolizumab and thiopurines was associated with lower treatment failure compared to vedolizumab monotherapy in CD but not UC across the US and France.