BackgroundRoxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor used to treat anemia in patients with chronic kidney disease (CKD); however, evidence from randomized trials has not fully clarified its associations with thrombotic outcomes and all-cause mortality.MethodsWe searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to 21 August 2025 for randomized controlled trials comparing roxadustat with placebo or erythropoiesis-stimulating agents (ESAs) in adults with CKD. The primary outcome was vascular access thrombosis (VAT), while the secondary outcomes were all-cause mortality, any venous thromboembolism (VTE), and adverse events (AEs) leading to treatment discontinuation. We used the random-effects model for primary analyses and conducted sensitivity analyses using the leave-one-out and fixed-effects models. Furthermore, certainty of evidence was assessed using the GRADE framework.ResultsTwenty randomized comparisons (involving 11,418 participants) were included in this study. Roxadustat was associated with higher odds of VAT (odds ratio (OR): 1.50; 95% confidence interval (CI): 1.06–2.12) and all-cause mortality (OR: 1.14; 95% CI: 1.06–1.22) with minimal heterogeneity; it was also found to increase AEs leading to discontinuation (OR: 1.76; 95% CI: 1.48–2.10). For any VTE, the estimate was imprecise and had a wide CI including the null value (OR: 3.69; 95% CI: 0.71–19.14). Subgroup analyses showed no evidence of effect modification for mortality by dialysis status or comparator type. For VAT, the subgroup estimates were directionally adverse for both the dialysis-dependent (DD) and non-dialysis-dependent (NDD) populations. However, the primary clinical interpretation of VAT pertained to the DD population because the majority of NDD patients lacked established vascular access; thus, the NDD findings warrant cautious interpretation. Discontinuation due to AEs increased in both the DD and NDD trials, with larger effects in the DD and ESA-controlled trials. Certainty of evidence was moderate for mortality and VAT but low for any VTE and AE-related discontinuation.ConclusionIn this meta-analysis of anemia in CKD, roxadustat was found to be associated with higher odds of VAT and all-cause mortality, along with increased AEs leading to treatment discontinuation, whereas the effects on any VTE remained uncertain because of imprecise results. These findings support careful selection of patients, close surveillance of hemoglobin levels after treatment initiation or dose adjustment, and continued monitoring of vascular access when using roxadustat in dialysis settings.