BACKGROUND: Up to 50 % of patients do not take medications as prescribed. Interventions to improve adherence are needed, with an understanding of which patients benefit most. OBJECTIVE: To test the effect of two low-literacy interventions on medication adherence. DESIGN: Randomized controlled trial, 2×2 factorial design. PARTICIPANTS: Adults with coronary heart disease in an inner-city primary care clinic. INTERVENTIONS: For 1 year, patients received usual care, refill reminder postcards, illustrated daily medication schedules, or both interventions. MAIN MEASURES: The primary outcome was cardiovascular medication refill adherence, assessed by the cumulative medication gap (CMG). Patients with CMG< 0.20 were considered adherent. We assessed the effect of the interventions overall and, post-hoc, in subgroups of interest. KEY RESULTS: Most of the 435 participants were elderly (mean age = 63.7 years), African-American (91 %), and read below the 9th-grade level (78 %). Among the 420 subjects (97 %) for whom CMG could be calculated, 138 (32.9 %) had CMG<0.20 during followup and were considered adherent. Overall, adherence did not differ significantly across treatments: 31.2 % in usual care, 28.3 % with mailed refill reminders, 34.2 % with illustrated medication schedules, and 36.9 % with both interventions. In post-hoc analyses, illustrated medication schedules led to significantly greater odds of adherence among patients who at baseline had more than eight medications (OR=2.2; 95 % CI, 1.21 to 4.04) or low self-efficacy for managing medications (OR=2.15; 95 % CI, 1.11 to 4.16); a trend was present among patients who reported non-adherence at baseline (OR= 1.89; 95 % CI, 0.99 to 3.60). CONCLUSIONS: The interventions did not improve adherence overall. Illustrated medication schedules may improve adherence among patients with low selfefficacy, polypharmacy, or baseline non-adherence, though this requires confirmation.KEY WORDS: coronary heart disease; medical adherence; medication management.