This study sought to define the ability of AMG 145, a monoclonal antibody directed against proprotein convertase subtilisin kexin type 9 (PCSK9), to enable subjects at high risk for major adverse cardiovascular events to achieve National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) parameters for low-density lipoprotein cholesterol (LDL-C) and other lipid goals. Many patients at high risk for adverse cardiovascular events are unable to achieve the NCEP-ATP III LDL-C goal of<70 mg/dl, even with high-potency statin therapy. In 282 subjects from the LAPLACE-TIMI 57 (LDL-C Assessment with PCSK9 monoclonaL Antibody Inhibition Combined With Statin thErapy-Thrombolysis In Myocardial Infarction 57) trial at high risk according to NCEP-ATP III criteria, we compared the proportion of subjects achieving the NCEP-ATP III recommended LDL-C goal of<70 mg/dl across treatment arms. Other outcomes included the triple goals of LDL-C<70 mg/dl, non-high-density lipoprotein cholesterol (HDL-C)<100 mg/dl, and apolipoprotein B (ApoB)<80 mg/dl. During the dosing interval, more than 90% of subjects in both of the top dose groups every 2 weeks and every 4weeks attained this lipid target over the dosing interval, with similar success rates for the triple lipid goal. PCSK9 inhibition with AMG 145 enables high-risk patients to achieve established lipid goals. If this therapy demonstrates efficacy for reducing cardiovascular events with a favorable safety profile in ongoing phase 3 trials, we believe it will have major public health implications.