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Introduction: There is limited evidence on the long-term persistence of antihypertensive therapy.Methods: We linked Medicare Part D Event data (2006 - 2012) for participants of the Chicago Heart Association Detection Project Industry Study (1967 - 1972) who were diagnosed with essential hypertension and had at least one drug (any drug) event (N = 5,578). Antihypertensive medications and therapeutic classes were identified using the Medi-Span Electronic Drug File v2. The adherence rate was defined by the proportion of days covered (PDC) in 6-month intervals from the first fill of antihypertensive medication and was calculated separately for each therapeutic class. Additionally, to identify adherence patterns as the number of medications an individual used increased, we calculated adherence rates for time intervals after each subsequent medication was filled. Fractional response generalized linear models were used to identify predictors of the adherence patterns.Results: At 6 months from the first fill, the median adherence rate was 0.72 and the mean was 0.56. Roughly 30% of the individuals in the sample did not fill any antihypertensive medication for the duration of the study. Adherence rates declined substantially over time, but the largest drop occurred within the first 12 months. Compared to individuals with a high school degree or less, individuals with more than a high school degree were on average 8.6% more adherent (p-value <0.001); however, they experienced similar drops in adherence rates over the 6-year duration. Similarly, the adherence patterns were parallel for white and non-white individuals over the study duration although white individuals had higher adherence rates. Moreover, as the number of medications prescribed increased, the overall adherence rates declined at an increasing rate. For example, average adherence rates decreased by 5.2% (p-value <0.001) as the number of medications increased from one to two and by 8.3% (p-value <0.001) as the number of medications increased from two to three.Conclusion: Adherence to antihypertensive therapy decreased significantly over time and with greater medication burden. Interventions are needed to improve persistence in antihypertensive therapy, particularly among those taking multiple medications.