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Prior work demonstrated significantly improved prescription label comprehension and functional health literacy (FHL) using an educational intervention and redesigned prescription label.The objective of this study was to assess the effectiveness of the educational intervention to improve prescription label understanding using three factors: (1) redesigned prescription label, (2) previously validated MLT and (3) pillbox fill test.English-speaking patrons ≥55 years old taking ≥2 prescription medications were recruited in this prospective, multisite, randomized, controlled, pre-post study, in California, Illinois, and Ohio. Participants completed the MLT (25 points) as a test of label comprehension and filled a 7 × 4 pillbox (Pillbox test, 35 points) at baseline and 1-month follow-up. The intervention group received tailored education by a student or pharmacist on how to read the label based on their response to the MLT and Pillbox Test.Combined data analysis was conducted of the 92 (63.4%) completed follow-ups from all sites. Baseline characteristics were comparable between control and intervention groups. Overall, mean MLT increased in both control and intervention groups (ΔPre-Post: +0.7 point vs. +0.8 point, p < 0.05). Although not statistically significant, pillbox test scores increased by 2.0 points in the intervention group compared to a slight decrease in the control group (−0.8 point, p > 0.05). Significant correlation between MLT and Pillbox scores was observed (r = 0.63, p < 0.05). Subgroup analysis between sites revealed that the CA-site had lower educational background and English proficiency; lower mean MLT and Pillbox Fill pre-scores compared to the IL- and OH-sites, with a statistically significant effect of intervention on MLT and Pillbox post-scores.This study extended earlier findings that focused education using redesigned Rx labels helped improve Rx label comprehension and observed action. Larger studies are needed to determine the impact on patient outcomes. Patients with lower education, English proficiency, and/or FHL may benefit from education that could translate into improved medication use behavior.