BACKGROUND AND OBJECTIVES: In literature, different methods of calculating persistence are used. In this study, the effect of using these different methods on persistence and the association of patients characteristics and persistence are assessed.METHODS: The PHARMO record linkage system was used to calculate persistence with antihypertensive drugs for a cohort of 14,466 new users of antihypertensives. Three different types of methods were used to define the maximum gap allowed between two prescriptions that a patient may have to be defined as a continuous user, one based on a defined number of days (varying from 9-365 days), the second based on the duration of the last prescription (varying from 0.1-4 times the duration), the third based on a combination of both methods, whichever leads to the lowest number of days. RESULTS: Refill persistence varied between 19.7-86.4% (method 1), between 27.9-90.2% (method 2), and between 19.7-86.4% (method 3). Furthermore, patient characteristics associatedwith persistence differed between and within the three different methods. CONCLUSION: The method used and the variation within a method influenced both persistence and the association between patient characteristics and persistence. Results of persistence studies are highly influenced by the researchers’ method of the maximum allowed treatment gap.