BACKGROUND: There have been no prior reports of detailed evaluations using intravascular imaging during Jetstream treatment. AIMS: This study, therefore, aimed to investigate the effects of calcification characteristics and wire bias on lumen gain in Jetstream atherectomy using optical frequency domain imaging (OFDI). METHODS: This study enrolled consecutive patients who underwent OFDI-guided Jetstream atherectomy with 1.85 mm, 2.4 mm blade down (BD), and 2.4 mm blade up (BU). Cross-sections were categorized into three groups based on OFDI findings before Jetstream atherectomy: fibrous plaques (FPs), calcified protrusions (CPs), and eruptive calcified nodules (ECNs). RESULTS: Twenty-seven patients (36 limbs) were enrolled, and 1502 cross-sections were serially analyzed. There were 186 FPs, 753 CPs, and 563 ECNs. The acquired lumen gain after all atherectomy steps was significantly larger in the ECNs group than in the CPs and FPs groups. ECNs had the strongest effect on the variability in the lumen gain. In the effect of wire bias on the degree of debulking, a significant correlation was observed between wire distance and lumen gain in 1.85- and 2.4-mm BD atherectomy procedures. However, in the 2.4-mm BU procedure, no significant correlation was recorded. CONCLUSIONS: Jetstream atherectomy for ECNs can result in greater lumen gain. In the 1.85- and 2.4-mm BD atherectomy procedures, wire bias may be involved in lumen gain, whereas in the 2.4-mm BU procedure, lumen gain is obtained regardless of wire bias. In Jetstream atherectomy procedures, a detailed assessment using OFDI may contribute to predicting the degree of debulking. TRIAL REGISTRATION: UMIN ID: UMIN000054588. https://center6.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000061997.