Background: Informed consent can be obtained by various methods, by various people, and with use of various types of consent forms. Persistent effort is necessary to reveal the practical realities of informed consent to improve ethical and legal standards. Objective: To determine the ethical challenges of obtaining informed consent from surgical patients. Methods: The present study was a descriptive cross-sectional study using two researcher-made questionnaires and a checklist for data collection. Data were collected from nursing personnel ( n = 95) and surgical patients ( n = 203) on the surgical wards of three university hospitals in Isfahan, Iran. Data were analyzed using descriptive statistics, Spearman’s rank correlation, Pearson’s correlation coefficient, and the t-test. Ethical considerations: The study was approved by the Ethics Committee of Isfahan University of Medical Sciences (No: 396478). Results: The mean scores (maximum 100) of awareness, competency, and authority were 36.3, 67.7, and 57.6, respectively. The overall quality of the informed consent was poor (score 53.9 of 100). The higher educational level in patients was correlated with lower awareness of and less authority to give informed consent. Only 12.6% of the nurses stated that patients were given sufficient information to assure informed consent. In 89.2% of the consent forms, the risks of the treatment were mentioned. However, alternative methods and risks and advantages of rejecting the treatment were not mentioned in any of the forms. Conclusion: Ethical challenges to obtaining informed consent include patients’ poor awareness of their rights, a failure to provide adequate information to patients, absence of consideration of patients’ educational level, an unclear definition of who is responsible for obtaining informed consent from the patients, time constraints, and use of unclear language and medical jargon. Constructing an ethical framework may guide nursing staff in dealing with the ethical challenges involved in obtaining informed consent.