Histopathologic studies have demonstrated that vessels enlarge to compensate for an increase in plaque burden; this has been confirmed in vivo using intravascular ultrasound (IVUS). The initial studies suggested a biphasic course of lesion formation with (1) preservation of lumen dimensions up to a plaque burden of approximately 40%, and (2) luminal narrowing as plaque burden further increases. In this study, we used IVUS and angiography to assess the extent of left main (LM) atherosclerosis in 107 patients undergoing catheter-based procedures of the left anterior descending or left circumflex coronary arteries. Using IVUS, atherosclerotic plaques were found in all LM arteries, but only 26 (24%) had varying degrees of luminal narrowing on the angiogram. Nevertheless, there was an inverse relation (r = −0.62, p <0.0001) between the minimal lumen area and the plaque burden (i.e., plaque + media divided by total vessel area) that was not restricted to plaque burden values >40% (or >30%), but persisted at plaque burden values of 20% to 40%. In addition, LM arteries with a plaque burden <40% had a similar total vessel area as did LM arteries with a plaque burden ≥40% (22.9 ± 6.1 vs 21.8 ± 4.8 mm², p = 0.30). These data suggest that lumen dimensions may not be preserved even if plaque occupies no more than 20% to 40% of the total vessel area. Thus, there is more variation in remodeling response during earlier stages of plaque accumulation within the LM artery than is commonly suggested.