Percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) by the antegrade approach is sometimes difficult, especially in the right coronary artery (RCA). We performed successful PCls following a retrograde approach via a septal branch in 2 patients with CTO in RCA. The method involves leading the retrograde guidewire outside the body through an opposite guiding catheter after the wire crosses the target lesion. A balloon or stent could then be delivered retrogradely or antegradely. Even a soft retrograde wire always crosses the lesion through the true lumen, as confirmed by IVUS. Selecting a suitable collateral, a straighter rather than a larger one, is crucial. Our results do not support the current concept regarding CTOs. Probably, the distal fibrous cap is soft and the proximal one has a thin point that soft wires, even blunt ones, can penetrate easily. The distal penetration point appears to connect to the proximal uncalcified thin point. Many channels seem to spread out from the proximal side, tree-like, within the lesion. In the retrograde approach, the wire is unlikely to enter these branch channels. The results suggest that PCI by the retrograde approach may be effective for treating CTOs of RCA.