Clinical decision support systems (CDSSs) differ from other health information systems in their aim to directly influence the decision-making behaviour of healthcare professionals. As a result, CDSSs face additional challenges with respect to user acceptance. The objective of this study was to investigate subjective usability of a guideline-based CDSS for outpatient cardiac rehabilitation. The system, named CARDSS, was previously found to be effective in improving guideline adherence of rehabilitation professionals in a cluster randomized trial. To assess CARDSS' usability, a modified version of the IBM Computer System Usability Questionnaire was sent to all 68 professionals from the 28 outpatient clinics that participated in the trial. The questionnaire was returned by 63 respondents (93%) from 27 clinics. Factors that influenced CARDSS' usability were identified using linear regression analysis. Analysis showed that professionals who managed to smoothly integrate the system with their daily routine were more satisfied with ease of system use. Furthermore, a positive attitude of respondents towards CDSSs in general and a better agreement with the content of the national guidelines were positively correlated to satisfaction with CARDSS' overall usability and each of its sub-domains.