Lead Author's Financial Disclosures Nothing to disclose. Study Funding None. Background/Synops Despite the beneficial effects of statins on progression of coronary atherosclerosis, significant cardiovascular (CV) risk persists in patients with residual hypertriglyceridemia. REDUCE-IT demonstrated that Icosapent ethyl (IPE) added to statins significantly reduced adverse CV outcomes in these patients. The EVAPORATE trial showed a significant reduction in coronary plaque progression in the IPE arm, offering mechanistic insights to the CV benefits of IPE. Circulating ceramide (CER) levels and CER ratios are important predictors of coronary plaque instability, progression, and adverse CV risk. Objective/Purpose We sought to compare the effect of IPE vs placebo on ceramide scores and ratios in participants enrolled in EVAPORATE trial. We further assessed correlations between CER levels and changes in coronary plaque burden and characteristics. Methods EVAPORATE is a randomized, placebo-controlled trial, using CCTA to evaluate the effects of IPE as an adjunct to statins on coronary plaque progression in a cohort with elevated triglycerides, over 18 months. A total of 63 participants from the EVAPORATE trial were included. Changes in serum levels of CER species, ratios, and scores were compared between patients receiving IPE vs placebo. Spearman's correlation was used to examine association of ceramide scores and changes in coronary plaque volumes. Results CER ratios and scores were similar between the groups at baseline. In the IPE group, the CER score was 4.27 (SD 3.02) at baseline and was 4.00 (SD 3.05) at follow-up (p=0.55). At 18 month follow-up, there was a significant increase in CER ratios, CER 16:0/24:0 and CER 18:0/24:0, in the placebo group (p=0.0018; p=0.0076, respectively), compared to no significant change in the IPE group (p=0.85; p=0.37, respectively). Changes in CER score did not correlate with changes in total plaque volumes in either group (IPE (r=0.326), placebo (r=-0.295) (p>0.05). Conclusions There were significant differences in the CER ratios in the IPE arm vs placebo arm in the EVAPORATE trial, as well as a trend to lowered CER score in the IPE group. Future studies are warranted to further characterize correlations of IPE and CER. Nothing to disclose.