Objective: Changes in carotid wall morphology (MORPH) and plaque composition (COMP) over 2 years (yrs) of intensive lipid therapy by plaque types were investigated in AIM-HIGH. Methods: Qualified baseline and 2-yr follow-up scans were obtained in 156 AIM-HIGH subjects. MR images were analyzed by independent Core Lab reviewers using published criteria for quantifications of MORPH and COMP. MORPH included volumes of total vessel (TVV), lumen (LV), wall (WV=TVV-LV) and fibrous tissue (FTV) in mm3 and %WV was calculated using the formula: (WV/TVV) X 100% in all available slices. COMP focused on percentages of lipid-rich necrotic core (%LRNC), FT (%FT) and calcium (%CA) calculated using the formula: (LRNC, FT or CA V/WV) x 100% using the slices containing LRNC. Of 156, 89 were in statin+placebo for extended-release niacin (ERN) and 67 in statin+ERN groups. Changes in MORPH and COMP were compared between the 2 treatment groups and between plaque types: w/o LRNC (n=76), w/ LRNC but w/o intraplaque hemorrhage (IPH) (n=62), w/ LRNC & IPH (n=18). Results: In the 76 subjects w/o LRNC, there were significant increases in TVV (24±52 mm3/yr, p Conclusions: Intensive lipid therapy with statin or statin plus ERN significantly associated with positive MORPH remodeling in plaques w/o LRNC. Plaques w/ LRNC experienced COMP improvement without significant MORPH changes. However, the COMP improvement was not seen in plaques w/ IPH. These results indicate that plaques in different disease stages respond to lipid therapy differently.