Objective Factors associated with treatment compliance have been well studied. However, no study has examined treatment compliance under the context of physician–industry relationship. This study developed a conceptual framework of physician–industry relationship and treatment compliance, and empirically tested patients' treatment compliance and affordability under the physician–industry relationship in the USA. Design We first proposed a conceptual framework to analyze different scenarios, where the physician–industry relationship could impact patients' treatment compliance and affordability, taking into consideration the role of health insurers. We then employed a nationally representative data set to investigate these relationships. Multivariable logistic regressions were employed to examine the physician–industry relationship and the physicians' perception of patients' treatment compliance. Setting and Participants 2008 Health Tracking Physician Survey. Results Our results showed that physicians with closer industry relationships were more likely to report rejection of care by insurers [odds ratios (ORs): 1.24–1.85, P < 0.001], patients' non-compliance with treatment (OR: 1.34, P < 0.01) and patients' inability to pay (OR: 1.42, P < 0.01) as the major problems affecting their ability to provide high quality care, when compared with physicians without industry relationships. Conclusions Our results shed light on the lack of articulation among industry, physicians and health insurers in the USA. It is important to make sure that different agents in the health-care marketplace, such as physicians, industry, and health insurers, coordinate more efficiently to provide quality and consistent care to patients. [ABSTRACT FROM PUBLISHER]