Background: Medication non-adherence is a complex health care problem. Due to non-adherence, substantial numbers of cardiovascular patients benefit from their medication to only a limited extent. In order to improve adherence, a variety of pharmacist-led interventions have been developed. However, even the most effective interventions achieved only a modest positive effect. To be effective, interventions should be targeted at underlying barriers to adherence, developed in a systematic manner and tailored to specific features of a target group and setting. The current paper describes the design of the Cardiovascular medication non-Adherence Tailored Intervention (CATI) study aimed to evaluate the (cost-)effectiveness of a patient-tailored intervention programme in patients using antihypertensive medication. Methods: The CATI study is a randomised controlled trial that will be performed in 13 community pharmacies. Patients aged 45-75 years using antihypertensive medication and considered non-adherent according to pharmacy dispensing data, as well according to a self-report questionnaire, are eligible to participate. Patients in the intervention condition will receive a patient-tailored, pharmacist-led intervention programme. This programme consists of a structured interview at the pharmacy to identify patients' barriers to adherence and to counsel patients in order to overcome these barriers. The primary outcome is self-reported medication adherence measured with the MARS-5 questionnaire. Secondary outcome measures are blood pressure, illness perceptions, quality of life and societal costs. A cost-effectiveness analysis and process evaluation will also be performed. Discussion: This study will provide insight into the (cost-)effectiveness of a patient-tailored, pharmacist-led intervention programme in non-adherent patients using antihypertensive medication. This intervention programme allows community pharmacists to support their patients in overcoming barriers to adherence and improving medication adherence in a structured and patient-tailored manner. An effective intervention will not only enhance medication adherence, but may also improve health outcomes and decrease health care utilisation and costs. Trial registration: Netherlands Trial Register (identifier: NTR5017), registered on 2 February 2015.