To compare the performance of conventional versus spectral-based electronic stool cleansing for iodine-tagged CT colonography (CTC) using a dual-layer spectral detector scanner. We retrospectively evaluated iodine contrast stool-tagged CTC scans of 30 consecutive patients (mean age: 69 ± 8 years) undergoing colorectal cancer screening obtained on a dual-layer spectral detector CT scanner. One reader identified locations of electronic cleansing artifacts (n = 229) on conventional and spectral cleansed images. Three additional independent readers evaluated these locations using a conventional cleansing algorithm (Intellispace Portal) and two experimental spectral cleansing algorithms (i.e., fully transparent and translucent tagged stool). For each cleansed image set, readers recorded the severity of over- and under-cleansing artifacts on a 5-point Likert scale (0 = none to 4 = severe) and readability compared to uncleansed images. Wilcoxon's signed-rank tests were used to assess artifact severity, type, and readability (worse, unchanged, or better). Compared with conventional cleansing (66% score ≥ 2), the severity of overall cleansing artifacts was lower in transparent (60% score ≥ 2, p = 0.011) andtranslucent (50% score ≥ 2, p < 0.001) spectral cleansing. Under-cleansing artifact severity was lower in transparent (49% score ≥ 2, p < 0.001) and translucent (39% score ≥ 2, p < 0.001) spectral cleansing compared with conventional cleansing (60% score ≥ 2). Over-cleansing artifact severity was worse in transparent (17% score ≥ 2, p < 0.001) and translucent (14% score ≥ 2, p = 0.023) spectral cleansing compared with conventional cleansing (9% score ≥ 2). Overall readability was significantly improved in transparent (p < 0.001) and translucent (p < 0.001)spectral cleansing compared with conventional cleansing. Spectral cleansing provided more robust electronic stool cleansing of iodine-tagged stool at CTC than conventional cleansing. • Spectral-based electronic cleansing of tagged stool at CT colonography provides higher quality images with less perception of artifacts than does conventional cleansing. • Spectral-based electronic cleansing could potentially advance minimally cathartic approach for CT colonography. Further clinical trials are warranted.