Background and aims: Significant macrophages infiltration in advanced atherosclerotic plaques promotes acute coronary events. Hence, the clinical imaging of macrophage content in coronary atherosclerotic plaques could potentially aid in identifying patients most at risk of future acute coronary events. The aim of this study was to introduce and validate a simple intravascular optical coherence tomography (IV-OCT) image processing method for automated, accurate and fast detection of macrophage infiltration within coronary atherosclerotic plaques. Methods: This method calculates the ratio of the normalized-intensity standard deviation (NSD) values estimated over two axially-adjacent regions of interest in an IV-OCT cross-sectional image (B-scan). When applied to entire IV-OCT B-scans, this method highlights plaque areas with high NSD ratio values (NSDRatio), which was demonstrated to be correlated with the degree of coronary plaque macrophage infiltration. Results: Using an optimized NSDRatio threshold value, coronary plaque macrophage infiltration could be detected with ~88% sensitivity and specificity in a database of 28 IV-OCT scans from postmortem coronary segments. For comparison, using an optimized NSD threshold value, considered the standard IV-OCT signature for macrophages, coronary plaque macrophage infiltration could be detected with only ~55% sensitivity and specificity. Conclusions: The proposed NSDRatio method significantly increases the sensitivity and specificity for the detection of coronary plaque macrophage infiltration compared to the standard NSD method. This computationally efficient method can be seamlessly implemented within standard IV-OCT imaging systems for in-vivo real-time imaging of macrophage content in coronary plaques, which could potentially aid in identifying patients most at risk of future acute coronary events.