OBJECTIVES Aliskiren is the first marketed direct renin inhibitor approved for the treatment of hypertension in 2007. Study objectives were to evaluate the utilization and persistence of aliskiren in a real-world setting. METHODS A retrospective cohort analysis was conducted using data from a large US pharmacy benefit manager who administers benefits to 27 million members nationally. Patients 18 years or older with at least two claims for aliskiren within a 12 month period of initiating treatment between April 2007 and October 2007 were included in the analysis. Patients also were required to be continuously enrolled in the same health plan 12 months prior to and 13 months after initiating aliskiren. Persistence on aliskiren, defined as time to discontinuation (ie, >30 day medication gap), was evaluated using a multivariate Cox proportional hazards model. Co-variates adjusted in the model included age, sex, comorbidities, geographical region, insurance type, copay, prescriber specialty and prior antihypertensive utilization. RESULTS A total of 1329 patients were identified as having received aliskiren. Mean patient age was 63.5 (s.d.=13) years and 52.3% were female. Most patients receiving aliskiren were not naïve to antihypertensive treatment. In the 12 months prior to initiating aliskiren, 90.1% of patients had received at least one other antihypertensive medication, and 57.3% had used 3 or more classes of antihypertensives. Mean persistence on aliskiren was 248 (s.d.=132) days. Multivariate analysis of persistence on aliskiren suggest that the risk of discontinuing was higher among those with copays ≥$50 relative to copays between $0 and $5 (Hazard ratio:1.74, 95% CI: 1.34-2.34). CONCLUSIONS Aliskiren is most used among patients previously treated with other antihypertensives and a lower pharmacy copay was an important factor associated with medication persistence. Additional research is needed to assess clinical implications of persistence.