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To assess adherence to medical treatment in patients with heart failure (HF) using a specific questionnaire and measurement of the serum concentration of digoxin.Forty patients with symptomatic HF and a clinical indication for digoxin were included in this pilot study. The assessment of adherence to the medical regime was based on two different methods: (i) the CARDIA-Questionnaire and (ii) the measurement of serum digoxin concentration (SDC) at 1 and 6 months. All patients were placed on digoxin treatment (target SDC 0.6–0.8 ng/mL) at baseline. Poor adherence was defined if the patient self-reported taking ≤75% of the prescribed HF medication or had an SDC < 0.4 ng/mL (subtherapeutic range) at the follow-up visits. During the entire follow-up, the proportion of patients with poor adherence was 15% as assessed by the questionnaire, 20% as assessed by the SDC, and 25% if both methods were combined.Although HF is a symptomatic disease, the proportion of patients with poor adherence to the medical regime in our study was high (up to 25%). The objective methodology based on the measurement of the SDC identified a higher number of patients with poor adherence when compared with the CARDIA-Questionnaire.