BackgroundCancer-associated thrombosis is a frequent complication of cancer; however, little evidence is available regarding the association between cancer history and coronary artery stent thrombosis (ST). We aimed to investigate the relationship between cancer history and second-generation drug-eluting stent thrombosis (G2-ST).MethodsFrom the REAL-ST (Retrospective Multicenter Registry of ST After First- and Second-Generation Drug-Eluting Stent Implantation) registry, this study evaluated 1265 patients (G2- ST cases,n= 253; controls,n= 1012) with cancer-related information available.ResultsThe prevalence of patients with cancer history was higher (12.3% vs. 8.5%,p= 0.065), and that of currently diagnosed and currently treated cancer was significantly higher in ST cases than controls (3.6% vs. 1.4%,p= 0.021; 3.2% vs. 1.3%,p= 0.037, respectively). Multivariable logistic regression analysis revealed that cancer history was associated with late ST (odds ratio [OR]: 2.80, 95% confidence intervals [CI]: 0.92–8.55,p= 0.071) and very late ST (OR: 2.40, 95% CI: 1.02-5.65,p= 0.046), but not with early ST (OR: 1.01, 95% CI: 0.51-2.00,p= 0.97). During the median follow-up period of 872 days after the index ST events, patients with cancer history showed a higher mortality than those without, among both ST cases (hazard ratio [HR]: 1.93, 95% CI: 1.06-3.51,p= 0.031) and controls (HR: 1.93, 95% CI: 1.09-3.40,p= 0.023).ConclusionA post hoc analysis of REAL-ST registry revealed that patients with G2-ST had a higher prevalence of currently diagnosed and currently treated cancer. Notably, cancer history was associated with the occurrence of late and very late ST, but not with early ST.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12959-023-00503-5.