Abstract: Background and Objective: Health and safety issues have always been a major problem and concern in the construction industry. Although much upgrading in construction safety has been achieved, the industry continues to lack behind most other industries about safety. Therefore, the purpose of this research was to study the possible effects of workers, organizations and environmental factors mediated by safety orientation on safety performance. Additionally, the need to introduce a framework that brings together all these factors is studied. Materials and Methods: A research instrument namely a questionnaire was used for this study validated by an expert. About 600 respondents were randomly selected from government and private construction industries and yielded a response rate of 430 (71.6% response rate). Data were analyzed using SPSS and AMOS to achieve the objectives, thus, descriptive statistics were used to analyze the study variables. Additionally, Correlational analysis and structural equation modelling (SEM) were used to examine the research hypotheses. Results: The finding showed that Worker factors and organizational factors have a significant impact on safety performance, however, environmental factors do not affect safety performance. In addition to that, safety orientation mediated the relationship between worker factors, organizational factors and safety performance, the outcome of this research will help to develop a framework of occupational health and safety in construction industries for safety performance in Iran. Conclusion: Thus, this research carries values to the minister of labor and social affairs in enhancing the policy on safety performance.