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Abstract Background Self-management support systems (SMSS) have been proposed for renal transplant patients to increase their autonomy and reduce the number of hospital visits. For the design and implementation of such systems, it is important to understand factors influencing patients’ acceptance of a SMSS. This paper aims to identify these key factors. Methods From literature, possible factors and related questionnaire items were identified. Afterwards, focus groups with experts and patients were conducted to adapt the items to the application domain. To investigate acceptance of a SMSS and the influencing factors, fifty renal transplant patients answered the questionnaire before and after using the SMSS for 4 months. Results All the questionnaire constructs had a satisfactory or higher level of reliability. After using the SMSS for 4 months, trust and performance expectancy could explain part of the variation in behavioural intention of using the SMSS, but not beyond the explanation given by patients’ affect towards the system, which accounted for 26% of the variance. Conclusions We anticipate that in future caregivers implementing a SMSS will benefit from taking steps to improve patients’ affect as this was found to correlate with patients use intention. Trial registration The study was registered in ToetsingOnline, a registry held by the Dutch Central Committee on Research Involving Human Subjects. The registration number is NL33387.058.11 , and the date of registration is 31st July 2012.