BackgroundLesion characteristics were shown to predict procedural success and outcomes in chronic total occlusion (CTO) recanalization. However, diverse techniques involved in these studies might cause potential heterogeneity.ObjectiveThe study aimed to test the impacts of lesion characteristics on CTO intervention with a pure antegrade wiring-based technique.Methods and ResultsWe studied consecutive 325 patients (64.5 ± 11.1 years, 285 men) with native CTO lesions intervened by a single operator with an antegrade-based technique between August 2014 and July 2020. Forty-seven patients with antegrade procedural failure (20 with pure antegrade wiring failure and 27 with back-up retrograde techniques) were compared to 278 patients with antegrade-only procedural success. With a median follow-up of 30.8 (16.1–48.6) months, 278 patients with procedural success were further assessed for target vessel failure (TVF: cardiac death, target vessel myocardial infarction [MI], and target lesion revascularization [TLR]). Patients with antegrade procedural success had a lower percentage of history with bypass graft (4 vs. 15%, p = 0.004) and lower Multicenter Chronic Total Occlusion Registry of Japan (J-CTO) score (2.1±1.3 vs. 3.4 ± 1.0, p < 0.001), when compared to those with antegrade failure. The J-CTO score was independently associated with procedural failure (odds ratio = 2.5, 95% CI = 1.8–3.4) in multivariate analysis. However, only clinical features, such as female gender (hazard ratio [HR] = 4.3, 95% CI = 1.4–13.1), estimated glomerular filtration rate <60 ml/min/1.73 m2 (HR = 3.2, 95% CI = 1.0–9.9), and old MI (HR = 4.5, 95% CI = 1.5–12.8), but not J-CTO score, could predict long-term TVF in multivariate Cox regression model.ConclusionThe feasibility of the antegrade guidewire-crossing technique for native CTO intervention was highly determined by lesion characteristics. With such a simpler technique, the prognostic impact of lesion complexity shown in studies with multiple recanalization techniques was negligible. This suggested antegrade true lumen tracking techniques deserved to be tried better even for CTO lesions with higher complexity.