Electronic health records (EHRs) have become ubiquitous in clinical practice. Given the rich biomedical data captured for a large panel of patients, secondary analysis of these data for health research is also commonplace. Yet, there are many caveats to EHR data that the researchers must be aware of, such as the accuracy of and motive for documentation, and the reason for patients’ visits to the clinic. The clinician—the author of the documentation—is thus central to the correct interpretation of EHR data for research purposes. In this study, I interviewed 11 physicians in various clinical specialties to bring attention to their view on the validity of research using EHR data. Qualitative, in-depth, one-on-one interviews were conducted with practicing physicians in inpatient and outpatient medicine. Content analysis using a data-driven, inductive approach to identify themes related to challenges and opportunities in the reuse of EHR data for secondary analysis generated seven themes. Themes that reflected challenges of EHRs for research included (1) audience, (2) accuracy of data, (3) availability of data, (4) documentation practices, and (5) representativeness. Themes that reflected opportunities of EHRs for research included (6) endorsement and (7) enablers. The greatest perceived barriers reflected the intended audience of the EHR, the interpretation and meaning of the data, and the quality of the data for research purposes. Physicians generally expressed more perceived challenges than opportunities in the reuse of EHR data for research purposes; however, they remained optimistic.