High-definition intravascular ultrasound (HD-IVUS) utilizing more than 80 MHz frequency to assess atherosclerotic plaque, can theoretically achieve an axial resolution of less than [Formula: see text]. However, the blood is a high-attenuation source at high frequency, which would affect the imaging quality. There has been no research evaluating the blood-induced influence on HD-IVUS imaging. And whether a temporary removal of blood is needed for HD-IVUS is unknown. In this study, an ultrahigh-frequency (100 MHz) ultrasound transducer was developed to evaluate the blood-induced attenuation for HD-IVUS imaging. A series of tungsten-wire phantom images in saline and blood at varying hematocrits were obtained. The images showed that blood did influence the ultrahigh-frequency imaging quality greatly. The signal-to-noise ratio (SNR) decrease by 71.7% in porcine whole blood compared to that in saline at the same depth of 2.3 mm. Moreover, the potential flushing schemes for HD-IVUS were studied in varying hematocrits. Three flushing agents commonly used in intravascular optical coherence tomography (IV-OCT) were investigated, including iohexol, mannitol, and dextran 5% and saline as the control group. The attenuation of blood in varying hematocrits/flushing agents was measured from 90 to 110 MHz. The result indicated dextran 5% was a suitable flushing agent for HD-IVUS due to its less signal attenuation compared to others.