OBJECTIVE: To evaluate the effectiveness of: the DrugFactsBox® format for presenting written medication information and the SMART (Strategic Memory Advanced Reasoning Training) Program designed to enhance gist reasoning ability. METHODS: We used a 2 x 2 factorial research design. 286 patients with rheumatoid arthritis were randomly assigned to one of four groups: DrugFactsBox® Only, DrugFactsBox® Plus SMART, Other Consumer Medication Information (CMI) Only, and Other CMI Plus SMART. Data were collected via telephone interviews and online questionnaires at four time points: Baseline and 6-weeks, 3-months, and 6-months following baseline. The primary outcome variable was Informed Decision-Making, defined as making a value-consistent decision concerning use of disease modifying antirheumatic drugs based on adequate knowledge. RESULTS: We found no main effects for the two interventions, either alone or in combination. However, there was a significant interaction between assignment to SMART/No SMART Program and Informed Decision-Making at baseline. Among participants in the SMART groups who did not meet the criteria for Informed Decision-Making at baseline, 42.5% met the criteria at the 6-month follow-up, compared to 23.6% of participants in the No SMART groups (Mean Difference=18.9, 95% CI=5.6, 32.2, p=0.007). This difference was driven by increased knowledge in the SMART groups. Among participants who met the criteria for Informed Decision-Making at baseline, the difference between the SMART and No SMART groups was not statistically significant. CONCLUSIONS: Participation in a theory-driven program to enhance gist reasoning may have a beneficial effect on Informed Decision-Making among patients with inadequate knowledge concerning therapeutic options.