Motivation: Key for the success of a self-management support system (SMSS) is the patients’ motivation and ability to understand and to adhere to its recommendations. Methods: Layering, nudging, emphaticizing, and focusing principles were applied for the development of a web-based SMSS prototype with two communication styles: (1) a guided style that provided more interpretation support and addressed emotional needs; and (2) a factual style that showed only measurement history, medical information, and recommendations. Forty-nine renal transplant patients with three different experience levels participated in a lab study, in which they used the system in imaginary scenarios to deal with three medical health situations (alright, mild concern, and concern).