Providing 24-hour services is an inevitable part of the health care system. Shift work and smoking are major risk factors for cardiovascular disease among nurses. This study aimed to investigate the effects of smoking and shift work on physiological parameters and blood factors among nurses. The present study was a cross-sectional study conducted among 300 nurses in Tehran's specialized and sub-specialized hospital in Tehran. To collect the data, the demographic questionnaire was used. A digital Blood Pressure Monitor and heart rate monitor were used to measure physiological parameters. Blood factors were collected from the results of medical records (Blood CBC). Finally, the data were analyzed using SPSS-20 software. The combined effects of shift work and smoking showed that for people who are smokers and work in shifts, systolic blood pressure and BMI have a significant difference with day workers. Mean diastolic blood pressure and heart rate in shift workers and smokers were slightly higher than those of working day and non-smokers. At the same time, statistical analysis did not show a significant relationship between the parameters (p> 0.05). The results also showed that the concentration of cholesterol and triglycerides in shift workers and smokers was significantly different from day workers and non-smokers (p <0.05). Due to the importance of nurses' health as the main foundation of the health system, it is necessary to carry out intervention programs as well as more detailed studies and research on the effects of shift work and smoking on physiological parameters and blood parameters with lifestyle control. Manuscript profile