© 2016 Elsevier Inc. Background and propose In coronary bifurcation lesions (CBL), hydrophilic guidewires used for side-branch (SB) protection can be withdrawn from underneath the stent easier than other wires. However, the safety of which has not been investigated. Methods/materials We performed scanning electron microscopic (SEM) examination of hydrophilic wires – the Whisper and Runthrough wires – used for SB protection during stenting and proximal optimization technique (POT) in 30 patients with CBL. The distal 15 cm of the wire was examined every 1 mm by SEM and 4500 segments were analyzed to investigate for wire fracture, polymer shearing (PS), and its correlations with post-stenting creatine kinase (CK)-MB release. Results SEM examination showed no evidence for wire fracture. The total area of PS and the largest defect on the wire were significantly larger with the Whisper wire versus the Runthrough wire (0.15 ± 0.04 mm2 vs. 0.026 ± 0.01 mm2 and 0.04 ± 0.05 mm2 vs. 0.01 ± 0.01 mm2; P < 0.05, respectively). The total length of PS and the longest defect on the wire were significantly longer with the Whisper wire vs. the Runthrough wire (12.1 ± 14.5 mm vs. 2.7 ± 3.0 mm and 2.9 ± 4.2 mm vs. 1.0 ± 1.2 mm; P < 0.05, respectively), but there were weak correlations between the extents of PS with CK-MB release. Conclusions Hydrophilic guidewires may be safely used for SB protection during stenting and POT in CBLs. The extent of PS was significantly greater with the Whisper wire than with the Runthrough wire, but its correlation with post-stenting CK-MB release was weak.