Background: Embedding Web-based interventions within physiotherapy has potential, but knowledge on patient adherence to these interventions is limited. Introduction: This study explores which patient-, intervention-, and environment-related factors are determinants of adherence to the online component of e-Exercise, a 12-week blended intervention for patients with hip and/or knee osteoarthritis. Methods: A convergent mixed methods study was performed, embedded within an ongoing trial. Quantitative data of 109 participants that received e-Exercise were used for negative binomial regression analysis. Adherence was defined as the number of online evaluated weeks. Next, semistructured interviews on factors related to adherence to the online component were analyzed. Results: Nineteen participants with missing outcome data because their program was not started were excluded. Of the 90 analyzed participants, 81.1% were evaluated for at least 8 weeks. Adherence was highest for participants with middle education, 1-5-year osteoarthritis duration, and participants who were physiotherapist recruited. The 10 analyzed interviews revealed that sufficient Internet skills, self-discipline, execution of the exercise plan, the intervention's usability, flexibility, persuasive design, added value, and acceptable required time, and research participation were linked to favorable adherence. Discussion: It is unknown if patients who adhered to the online component also adhered to their exercise plans. The relationship between adherence to the online component and clinical outcomes will be addressed in a future study. Conclusions: The majority of the participants adhered to the online component of e-Exercise, illustrating its applicability. The integration within the physiotherapy setting and intervention's persuasive design appear to have an important role in optimizing patient adherence.