Use of dipeptidyl peptidase-4 (DPP-4) inhibitors, on the basis of spontaneous adverse event reports, has recently been suspected of causing splanchnic vein thrombosis. Here, we report the results of a population-based new-user active comparator cohort study addressing this hypothesis, comparing DPP-4 inhibitor initiators (n = 75 042) with initiators of glucagon-like-peptide-1 receptor agonists (GLP-1RAs) or sodium-glucose co-transporter-2 (SGLT2) inhibitors (n = 38 718). We estimated the hazard ratio (HR) associating DPP-4 inhibitor use with risk of splanchnic vein thrombosis using Cox regression. In a crude analysis, the incidence rate of splanchnic vein thrombosis was 0.22/1000 person-years among DPP-4 inhibitor initiators, compared to 0.17 among GLP-1RA/SGLT2 inhibitor initiators, corresponding to an unadjusted absolute incidence rate difference of 0.05 (95% confidence interval [CI] –0.04 to 0.14) and an HR of 1.29 (95% CI 0.78 to 2.15). Adjusting for potential confounders using stabilized inverse probability of treatment weighing, we obtained an absolute incidence rate difference of 0.03/1000 person-years (95% CI –0.07 to 0.14) and an HR of 1.18 (95% CI 0.62 to 2.26). No evidence of increased risk of splanchnic vein thrombosis was found in supplementary analyses, including an absence of any dose–response patterns. As such, we found no association between DPP-4 inhibitor use and splanchnic vein thrombosis risk.