Background: Nurses’ behavior in Educational-Medical centers is very important for improving the condition of patients. Ethical climate represents the ethical values and behavioral expectations. Attitude of people toward religion is both intrinsic and extrinsic. Different ethical climates and attitude toward religion could be associated with nurses’ behavior. Aim: To study the mediating effect of ethical climate on religious orientation and ethical behaviors of nurses. Research design: In an exploratory analysis study, the path analysis method was used to identify the effective (...) variables on ethical behavior. Participants/context: The participants consisted of 259 Iranian nurses from Hamadan University of Medical Sciences. Ethical considerations: This project with an ethical code and a unique ID IR.UMSHA.REC.1395.67 was approved in the Research Council of Hamadan University of Medical Sciences. Findings: The beta coefficients obtained by regression analysis of perception of ethical climate of individual egoism (B = −0.202, p < 0.001), individual ethical principles (B = −0.184, p = 0.001), local egoism (B = −0.136, p = 0.003), and extrinsic religious orientation (B = −0.266, p = 0.007) were significant that they could act as predictors of ethical behavior. The summary of regression model indicated that 0.27% of ethical behaviors of nurses are justified by two variables: ethical climate and religious orientation. Discussion and conclusion: Intrinsic religious orientation has the most direct impact and then, respectively, the variables of ethical climate of perceptions in the dimensions of individual egoism, individual ethical principles, local egoism, global ethical principle, and ethical behavior and extrinsic religious orientation follow. All the above, except global ethical principles and intrinsic orientation of religion have a negative effect on ethical behavior and can be predictors of ethical behavior. Therefore, applying strategies to promote theories of intrinsic religious orientation and global ethical principles in different situations of nursing is recommended. (shrink)