Background Few adults at high risk for atherosclerotic cardiovascular disease events use a PCSK9i (proprotein convertase subtilisin/kexin type 9 inhibitor). Methods and Results Using data from the US Veterans Health Administration, we identified veterans who initiated a PCSK9i between January 2018 and December 2019, matched 1:4 to veterans who did not initiate this medication over this time period (case‐cohort study). Two cohorts of veterans were analyzed: (1) atherosclerotic cardiovascular disease, with a most recent low‐density lipoprotein cholesterol (LDL‐C) ≥70 mg/dL; and (2) severe hypercholesterolemia (ie, familial hypercholesterolemia or any prior LDL‐C ≥190 mg/dL, with most recent LDL‐C ≥100 mg/dL). Conditional logistic regression was used to analyze factors associated with PCSK9i initiation, adjusting for all factors, simultaneously. There were 2394 initiators and 9576 noninitiators in the atherosclerotic cardiovascular disease cohort (median LDL‐C, 141 and 96 mg/dL, respectively; P <0.001). Factors associated with a higher likelihood of PCSK9i initiation included age 65 to <75 versus <65 years, highest versus lowest quartile of median area‐level income, familial hypercholesterolemia, former statin use, and current ezetimibe use. PCSK9i initiation was lower among veterans of a race/ethnicity other than non‐Hispanic White. There were 245 initiators and 980 noninitiators in the severe hypercholesterolemia cohort (median LDL‐C, 183 and 151 mg/dL, respectively; P <0.001). Age ≥75 versus <65 years, history of chronic kidney disease, former statin use, and current ezetimibe use were associated with a higher likelihood of PCSK9i initiation. Conclusions Several patient‐level factors, including age, sex, and race/ethnicity, were significantly associated with PCSK9i initiation, suggesting an unmet treatment need in several patient groups.