OBJECTIVES: To evaluate influences of prescription drug benefit parameters on participant adherence to drug therapies for chronic conditions. METHODS: Deidentified pharmacy claims were analyzed for participants continuously eligible from January 1 to December 31, 2003 and treated for diabetes, hypertension or hypercholesterolemia. Participants were grouped according to plan design: 201,179 diabetics in 666 groups; 535,446 hypercholesterolemia participants in 845 groups; and 877,918 hypertension participants in 940 groups. Based on a combination of compliance and persistency, average adherence was calculated for each group. Multivariate linear regression analyses were performed for the conditions, controlling for demographics and comorbidities. RESULTS: Analyses showed consistent effects of plan design parameters on adherence across the conditions. While major plan design changes intended to drive mail utilization may cause initial therapy disruption, resulting in short-term decreases in adherence (parameter estimate (PE) between -.046 and -.025, p<0.0001), overall higher mail utilization improves adherence consistently across conditions (PE between .043 and .062, p