Abstract. Intravascular near-infrared fluorescence (NIRF) imaging offers a new approach for characterizing atherosclerotic plaque, but random catheter positioning within the vessel lumen results in variable light attenuation and can yield inaccurate measurements. We hypothesized that NIRF measurements could be corrected for variable light attenuation through blood by tracking the location of the NIRF catheter with intravascular ultrasound (IVUS). In this study, a combined NIRF-IVUS catheter was designed to acquire coregistered NIRF and IVUS data, an automated image processing algorithm was developed to measure catheter-to-vessel wall distances, and depth-dependent attenuation of the fluorescent signal was corrected by an analytical light propagation model. Performance of the catheter sensing distance correction method was evaluated in coronary artery phantoms and ex vivo arteries. The correction method produced NIRF estimates of fluorophore concentrations, in coronary artery phantoms, with an average root mean square error of 17.5%. In addition, the correction method resulted in a statistically significant improvement in correlation between spatially resolved NIRF measurements and known fluorophore spatial distributions in ex vivo arteries (from r ¼ 0.24 to 0.69, p < 0.01, n ¼ 6). This work demonstrates that catheter-to-vessel wall distances, measured from IVUS images, can be employed to compensate for inaccuracies caused by variable intravascular NIRF sensing distances.