<b><i>Aim:</i></b> To develop a Web-based self-care program for patients after total laryngectomy according to a participatory design approach. <b><i>Methods:</i></b> We conducted a needs assessment with laryngectomees (n = 9) and their partners (n = 3) by means of a focus group interview. In 4 focus group sessions, a requirement plan was formulated by a team of health care professionals (n = 10) and translated into a prototype. An e-health application was built including illustrated information on functional changes after total laryngectomy as well as video demonstrations of skills and exercises. Usability of the prototype was tested by end users (n = 4) and expert users (n = 10). Interviews were held to elicit the intention to use and the desired implementation strategy. <b><i>Results:</i></b> Six main self-care topics were identified: (1) nutrition, (2) tracheostomy care, (3) voice prosthesis care, (4) speech rehabilitation, (5) smell rehabilitation, and (6) mobility of head, neck, and shoulder muscles. Expert users expressed concerns regarding tailored exercises, indicated a positive intent to implement the intervention in routine care, and expressed a need for guidance when implementing the intervention. End users and expert users appreciated the content completeness and multimedia-based information built into the application. <b><i>Conclusion:</i></b> The participatory design is a valuable approach to develop a self-care program to help meet users' needs.