Background: Moral distress is a stress symptom arising from situations that involve ethical dimensions where the health-care provider believes that he or she is unable to preserve all interests and values at stake. The aims of this study were to evaluate the impact of, and identify possible differences in, moral distress in podiatric physicians in the United States and Spain and to determine the ethical principles most closely related to moral distress. Methods: A 2008 e-mail survey of 93 US podiatric physicians and 93 Spanish podiatric physicians (N = 186) presented statements about different ethical dilemmas, values, and goals in the workplace. Results: Although moral distress is strongly present across the sample for all of the questions, the US sample shows higher levels of any kind of moral distress concerning questions about patients’ treatment and economic constraints, overload of paperwork, and acting against one’s conscience. In the US sample, 91.4% of physicians agreed mostly or completely with the statement that they often had to compromise their own values to cope with the demands of the workplace; 89.25% of US podiatric physicians indicated that their own professional values were congruent with the values of the organization; and a similar percentage (77.5%) reported a strong identification with the goals and framework of their work organization. The Spanish sample had similar results. Conclusions: The results underline the significance of moral distress for both samples, mainly related to time constraints and organizational aspects concerning patients and lack of resources. (J Am Podiatr Med Assoc 102(1): 57–63, 2012)