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Despite substantial healthcare costs, patient outcomes are sub-optimal in the United States and Canada compared to other countries that spend proportionally less on healthcare. This has led to recognition of the need to improve healthcare value, utilization of tools including clinical practice guidelines and development of initiatives such as the Choosing Wisely Campaign to achieve this goal. In spite of the intuitive appeal of these interventions designed to increase physician awareness of evidence and empower patients to engage in shared decision-making, they have had limited success in changing practice and physician prescribing behaviours. Using a mixed-methods approach, this thesis represents a purposeful attempt to understand the failure of existing approaches through an examination of the factors that influence clinical decision making. Specifically, the thesis integrates quantitative and qualitative methodologies to develop a deeper understanding of clinical decision-making. Consisting of a clinical vignette based survey, the quantitative study explores decision-making in four specific commonly encountered case contexts. After choosing the preferred management option, participants rated the influence of different factors on their decisions. Follow-up questions explored knowledge, attitudes and practices regarding incorporating cost considerations into decision-making. The results of the study were explored further in the qualitative component of the mixed study. The results indicate that clinical decision-making is influenced by an interrelated set of socioecological factors with evidence and clinical practice guidelines playing a secondary role. Because lack of knowledge is not a major factor in guideline discordant care, strategies to improve knowledge will have minimal effect in improving care. The qualitative study included an inquiry into the need for teaching and learning on the topic of cost and cost-effectiveness and sought input from physicians working in diverse settings on methods and topics that need to be included in medical education. The contributions of this thesis include a deeper understanding of the factors that influence clinical decision-making and suggestions for enhancing medical education. / Thesis / Doctor of Philosophy (PhD) / Despite the highest health-care expenditure in the world, patient health outcomes are suboptimal in the United States (US). Additionally, out-of-pocket patient costs are increasingly a cause of financial distress to American patients. Although Canada spends comparatively less than the US on healthcare, it is one of the top ten countries for healthcare spending as a proportion of the gross domestic product. In spite of this level of spending, patient outcomes in the US and Canada are worse when compared to many other economically developed countries that spend relatively less on healthcare. A substantial portion of healthcare spending is for services that do not improve patient outcomes while services proven to improve patient outcomes are underused. Utilizing sequential quantitative and qualitative studies this thesis is a purposeful attempt to identify and examine the factors that influence clinical decision making by physicians. The knowledge gained in this study may help inform the development and evaluation of strategies targeted at increasing adoption of evidence-based practices leading to improved health-outcomes at affordable costs.