Lower health literacy is associated with poorer health outcomes. Few interventions poised to mitigate the impact of health literacy in hypertensive patients have been published. We tested if a multi-level quality improvement intervention could differentially improve Systolic Blood Pressure (SBP) more so in patients with low vs. higher health literacy.We conducted a non-randomized prospective cohort trial of 525 patients referred with uncontrolled hypertension. Stakeholder informed and health literacy sensitive strategies were implemented at the practice and patient level. Outcomes were assessed at 0, 6, 12, 18 and 24 months.At 12 months, the low and higher health literacy groups had statistically significant decreases in mean SBP (6.6 and 5.3 mmHg, respectively), but the between group difference was not significant (Δ 1.3 mmHg, P = 0.067). At 24 months, the low and higher health literacy groups reductions were 8.1 and 4.6 mmHg, respectively, again the between group difference was not significant (Δ 3.5 mmHg, p = 0.25).A health literacy sensitive multi-level intervention may equally lower SBP in patients with low and higher health literacy. Practical health literacy appropriate tools and methods can be implemented in primary care settings using a quality improvement approach.