Introduction: Treatment of uncontrolled arterial hypertension reduces the risk of cerebral small vessel disease (CSVD) progression, though it is unclear whether this reduction occurs due to blood pressure control or antihypertensive class-specific pleotropic effects. The goal of this study was to investigate the influence of antihypertensive medication class on accumulation of white matter hyperintensities (WMH), a radiographic marker of CSVD, within a cohort with well-controlled hypertension. Methods: Using the SPRINT-MIND dataset, we completed a post-hoc analysis of participants who completed a baseline and 4-year follow-up brain MRI with volumetric WMH data. Antihypertensive medication data were recorded at follow-up visits between the MRIs. A percentage of follow-up time participants were prescribed each of the eleven classes of antihypertensive was then derived. Progression of CSVD was calculated as the difference in WMH volume between two scans and, to address skew, dichotomized into a top tertile (greatest) accumulation and combined middle and bottom tertiles (slowest) accumulation. Results: Among 448 individuals included in this study, vascular risk profiles were similar across WMH progression subgroups except age (70.1±7.9 years versus 65.7±7.3 years, p<0.001) and systolic blood pressure (128.3±11.0 mmHg versus 126.2±9.4 mmHg, p=0.039). The high had a mean WMH progression of 4.7±4.3 mL compared with 0.13±1.0 mL for the slowest progressors (p<0.001). Only angiotensin converting enzyme inhibitors (ACE-I) (OR 0.34, 95% CI 0.15-0.75, p=0.008) and dihydropyridine calcium channel blockers (d-CCB) (OR 0.39, 95% CI 0.19-0.81, p=0.012) were independently associated with lower odds of being in the greatest progression grouping. Conclusions: Amongst hypertensive participants in the SPRINT-MIND trial, ACE-I and d-CCB antihypertensive medications were associated with significantly lower odds of being in the highest tertile of WMH progression compared with other antihypertensive classes, independent of blood pressure control.