Background: Telemedicine is a rapidly evolving field that uses information and communication technology to provide remote health care services, such as diagnosis, treatment, consultation, patient monitoring, and medication delivery. With advancements in technology, telemedicine has become increasingly popular during the COVID-19 lockdown and has expanded beyond remote consultations via telephone or video to include comprehensive and reliable services. The integration of telemedicine platforms can enable patients and health care providers to communicate more efficiently and effectively., Objective: This study aims to investigate the awareness, knowledge, requirements, and perceptions of health care practitioners in Saudi Arabia during the pandemic health crisis from the end-user perspective. The findings of this study will inform policy makers regarding the sustainability of telemedicine and how it affects the process of provision of health care and improves the patients' journey., Methods: This study adopted a mixed methods design with a quantitative-based cross-sectional design and qualitative interviews to assess the perceptions of various health care professionals working in outpatient departments that have a telemedicine system that was used during the COVID-19 pandemic. For both approaches, ethics approval was obtained, and informed consent forms were signed. In total, 81 completed questionnaires were used in this study. In the second phase, general interviews were conducted with managerial staff and health care professionals to obtain their view of telemedicine services in their hospitals., Results: The study revealed that most participants (67/81, 83%) were familiar with telemedicine technology, and the study proved to be statistically significant at P<.05 with a proportion of the participants (52/81, 64%) believing that continuous training was essential for its effective use. The study also found that consultations (55/153, 35.9%) and monitoring patients (35/153, 22.9%) were the major components of telemedicine used by health care professionals, with telephones being the most commonly used mode of interaction with patients (74/117, 63.2%). In addition, 54% (44/81) of the respondents expressed concerns about patient privacy and confidentiality, highlighting this as a major issue. Furthermore, the majority of participants (58/81, 72%) reported the necessity of implementing national standards essential for telemedicine technology in Saudi Arabia. The interviews conducted as part of the study revealed 5 major themes: culture, barriers and difficulties, communication, implementation, and evaluation. These themes highlighted the importance of a culture of acceptance and flexibility, effective communication, and ongoing evaluation of telemedicine technologies in health care systems., Conclusions: This study provides a crucial message with insights into the perceptions and experiences of health care professionals with telemedicine during the COVID-19 pandemic in Saudi Arabia., (©Heba Alqurashi, Rafiuddin Mohammed, Amany Shlyan AlGhanmi, Farhan Alanazi. Originally published in JMIR Formative Research (https://formative.jmir.org), 28.09.2023.)