BackgroundIn the physician-patient relationship, patients’ uncertainty about diseases and the lack of trust in physicians not only hinder patients’ rehabilitation but also disrupt the harmony in this relationship. With the development of the web-based health industry, patients can easily access web-based information about health care and physicians, thus reducing patients’ uncertainty to some extent. However, it is not clear how patients’ web-based health information–seeking behaviors reduce their uncertainty.ObjectiveOn the basis of the principal-agent theory and the perspective of uncertainty reduction, this study aims to investigate the mechanism of how web-based disease-related information and web-based physician-related information reduce patients’ uncertainty.MethodsA web-based survey involving 337 participants was conducted. In this study, we constructed a structural equation model and used SmartPLS (version 3.3.3; SmartPLS GmbH) software to test the reliability and validity of the measurement model. The path coefficients of the structural model were also calculated to test our hypotheses.ResultsBy classifying patients’ uncertainties into those concerning diseases and those concerning physicians, this study identified the different roles of the two types of patients’ uncertainty and revealed that web-based disease-related information quality and web-based physician-related information can act as uncertainty mitigators. The quality of disease-related information reduces patients’ perceived information scarcity about the disease (β=−.588; P<.001), and the higher the information scarcity perceived by patients, the higher their uncertainty toward the disease (β=.111; P=.02). As for physician-related information, web-based word-of-mouth information about physicians reduces patients’ perceived information scarcity about the physician (β=−.511; P<.001), mitigates patients’ fears about physician opportunism (β=−.268; P<.001), and facilitates patients’ trust (β=.318; P<.001). These factors further influence patients’ uncertainty about the physician. In addition, from the test of mediating effect, patients’ trust in the physician fully mediates the relationship between their perceived information scarcity about the physician’s medical service and their uncertainty about the physician. Patients’ trust also partially mediates the relationship between their fear of the physician’s opportunism and their uncertainty about the physician. As for the two different types of uncertainty, patients’ uncertainty about the physician also increases their uncertainty about the diseases (β=.587; P<.001).ConclusionsThis study affirms the role of disease-related web-based information quality and physician-related web-based word-of-mouth information in reducing patients’ uncertainties. With regard to the traits of principal-agent relationships, this study describes the influence mechanism based on patients’ perceived information scarcity, fears of physicians’ opportunism, and patients’ trust. Moreover, information about physicians is effective in reducing patients’ uncertainties, but only if the information enhances patients’ trust in their physicians. This research generates new insights into understanding the impact of web-based health information on patients’ uncertainties.