Introduction: For patients with a chronic disease, the appropriate use of medication is the key to manage their illness. Adherence to medication is therefore important. Adherence can be divided into three parts: the initiation part, the execution phase, and the discontinuation part. Little is known about the determinants of the initiation part. For this reason, we describe the conduct of a stepwise procedure to study determinants of medication initiation for patients with a chronic disease. Methods/design: The stepwise procedure comprises of eliciting a list of all potential determinants via literature review, interviewing patients, and consulting an expert panel. This is followed by embedding the determinants in a theoretical framework, developing a questionnaire, and choosing adherence measurement methods. The consecutive steps that we conducted for the development of a tool for the prediction of adherence in our study sample of early arthritis patients are described. Discussion: Although we used a thorough procedure, there are still some pitfalls to take into account, such as the choice of theoretical framework. A strength of this study is that we use multiple adherence measurement methods and that we also take clinical outcomes into account.