This study adds to the currently limited evidence base on the efficacy of interventions targeting non-college-ready high school students by examining the impact of Kentucky’s Targeted Interventions (TI) program. We focus on interventions that students received under TI in the senior year of high school based on their 11th grade ACT test scores. Using difference-in-regression discontinuity and difference-in-difference designs with seven cohorts of 11th grade students, we find that, for an average per-student cost of about $600, TI significantly reduces the likelihood that students enroll in remedial course in both 2- and 4-year postsecondary institutions by 5–10 percentage points in math and 3–4 percentage points in English. These effects are similar among students who are eligible for free-or reduced-price lunch, Black and Hispanic students, students with remediation needs in multiple subjects, and students in lower-performing schools. Evidence also shows that TI increases the likelihood that students enroll in and pass college math before the end of the first year by four percentage points in 4-year universities. However, little evidence exists for TI affecting credit accumulation or persistence.