Background Therapeutic inertia (TI), failure to intensify antihypertensive medication when blood pressure (BP) is above goal, remains prevalent in hypertension management. The degree to which self‐reported antihypertensive adherence is associated with TI with intensive BP goals remains unclear. Methods and Results Cross‐sectional analysis was performed of the 12‐month visit of participants in the intensive arm of SPRINT (Systolic Blood Pressure Intervention Trial), which randomized adults to intensive (<120 mm Hg) versus standard (<140 mm Hg) systolic BP goals. TI was defined as no increase in antihypertensive regimen intensity score, which incorporates medication number and dose, when systolic BP is ≥120 mm Hg. Self‐reported adherence was assessed using the 8‐Item Morisky Medication Adherence Scale (MMAS‐8) and categorized as low (MMAS‐8 score <6), medium (MMAS‐8 score 6 to <8), and high (MMAS‐8 score 8). Poisson regressions estimated prevalence ratios (PRs) and 95% CIs for TI associated with MMAS‐8. Among 1009 intensive arm participants with systolic BP >120 mm Hg at the 12‐month visit (mean age, 69.6 years; 35.2% female, 28.8% non‐Hispanic Black), TI occurred in 50.8% of participants. Participants with low adherence (versus high) were younger and more likely to be non‐Hispanic Black or smokers. The prevalence of TI among patients with low, medium, and high adherence was 45.0%, 53.5%, and 50.4%, respectively. After adjustment, neither low nor medium adherence (versus high) were associated with TI (PR, 1.11 [95% CI, 0.87–1.42]; PR, 1.08 [95% CI, 0.84–1.38], respectively). Conclusions Although clinician uncertainty about adherence is often cited as a reason for why antihypertensive intensification is withheld when above BP goals, we observed no evidence of an association between self‐reported adherence and TI.