A retrograde approach through collateral channels is thought to improve the success rate of percutaneous coronary intervention for chronic total coronary occlusion (CTO). Among CTO lesions, the in-stent chronic total reocclusion (ISR-CTO) is a subset with an unsatisfactory outcome despite repeated procedures. Various strategies and techniques are required to improve the success rate of this novel approach. We describe a case in which a long ISR-CTO was successfully recanalized by a drug-eluting balloon after antegrade ballooning of the proximal part of the lesion with retrograde wire crossing, and discuss the availability of this approach for the treatment of long ISR-CTO.