Objective: This study was designed to explore the uncertainty in illness during the perioperative period for patients undergoing heart valve surgeries and analyze the related factors. Methods: A total of 162 patients who have received heart valve surgeries were selected as subjects. General information investigation scale, self-efficacy evaluation scale, medical coping modes questionnaire and Connor-Davidson resilience scale were used to gather relevant information before operation, while Mishel uncertainty in illness scale (MUIS) was used one day before operation and one day before hospital discharge to assess the level of illness uncertainty in patients and analyze relevant influential factors. Results: The scores of ambiguity, complexity, deficit information and unpredictability and total MUIS score for patients one day before hospital discharge were significantly lower than those for patients one day before operation (P<0.001). Age, years of education, average monthly family income, marital status, number of heart valve surgeries, complications and self-efficacy had significant effects on patients' perception of uncertainty in illness before operation (P<0.05). Pearson correlation analysis showed that there was a significant negative correlation between the total MUIS score one day before operation and resilience, self-reliance, optimism, confrontation, resignation, utilization of support, objective support and total social support (P<0.05), and there was a significant positive correlation between the total MUIS score and avoidance (P<0.05). Multivariate logistic regression analysis showed that age, years of education, number of heart valve surgeries, monthly family income, self reliance, optimism, confrontation and resignation were important risk factors for illness uncertainty in patients before operation (P<0.05). Conclusion: The illness uncertainty felt by patients undergoing heart valve surgeries is at a medium level. Age, education background, number of heart valve surgeries, monthly family income, psychological resilience and coping modes are main factors affecting illness uncertainty in patients.