Flexibility is typical of open universities and their e-learning designs. While it constitutes their main attraction, promising learners will be able to study “anytime anyplace”, it is also a cause for student dropout, demanding more self-regulation and engagement. This case study explored the professors’ experiences of flexibility in e-learning design and continuous assessment, and their perception of the risks and opportunities that more flexibility would imply for persistence and dropout. In-depth interviews with 18 full professors, who are the e-learning designers of undergraduate courses at the Open University of Catalonia (UOC), were analyzed employing qualitative content analysis. In the professors’ voices, the main causes for dropout are mainly student-centered yet connected to learning design: workload and time availability, student expectations, profiles, and time management skills. In their view, flexibility has both positive and negative effects. Some are conducive to engagement and persistence: improvement of personalized feedback, formative assessment, and module workload; while others generated resistance: more flexibility may increase workload, procrastination, dropout, and risk of losing professorial control, and be a threat to educational standards and quality. Untangling the tensions between dropout and flexibility may enhance learning design and educational practices that prevent student dropout. Stakeholders should focus on measures perceived as positive, such as assessment extension, personalized feedback and monitoring, and calibration of course workload. As higher education is globally turning to online delivery, due to the viral pandemic, such findings may be useful in both hybrid and fully online educational contexts.