Background: Job burnout, defined as a syndrome derived from prolonged exposure to stressors at work, is often observed in health care workers. Shift work and job satisfaction are considered two of the occupational risks for burnout in nurses. Nurses have stress and health complaints. In addition, nurses are likely to job burnout. Objectives: The current study aimed to determine the prevalence of job burnout and its association with work schedules and job satisfaction among Iranian nurses in a public hospital. Methods: This cross-sectional study was conducted in one of the largest Iranian public hospitals among 362 nurses (response rate: 80.44%) in Tehran, Iran. The Maslach burnout inventory (MBI-22) and demographic factors questionnaire were used in the present study. The relationship between job burnout with work schedules and job satisfaction was investigated with multiple logistic regression analysis. Results: The mean age and work experience of the participants were 36.14 ± 8.59 and 15.23 ±9.30 years, respectively. The result indicated a relatively high prevalence of burnout (particularly, personal accomplishment) among the study population. In general, 64.4% of participants reported low personal accomplishment level. The nurses engaged in shift work reported higher levels of emotional exhaustion (odds ratio (OR) = 1.02, 95% confidence interval (CI) = 1.006-1.041, P-value = 0.008); there was no relationship between work schedules with depersonalization and personal accomplishment. The result showed significant relationship between job satisfaction and emotional exhaustion (OR = 0.945, 95% CI = 0.928-0.963, P-value < 0.001) and personal accomplishment (OR = 1.003, 95% CI = 1.014-1.058, P-value = 0.001). Conclusions: The current study revealed that the Iranian nurses are exposed to a considerable risk of personal accomplishment. Also, job burnout is in association with shift working and low job satisfaction level. In this regard, working pressure, type of job and income may affect job burnout. Ergonomic interventional programs are recommended to improve the working conditions.