Frequent nursing errors are considered as factors that affect the quality of healthcare of patients. Capable nurses who are compatible with work conditions are more focused on their tasks, and this reduces their errors and cognitive failures. Therefore, this study was conducted with the aim of investigating the relationship between work ability index (WAI) and cognitive failures (CFs) as well as some factors that affect them in nurses working in the ICU, CCU, and emergency wards.This descriptive-analytical and cross-sectional study was conducted with 750 nurses at educational hospitals affiliated with the Tehran University of Medical Sciences in 2015. A questionnaire of work ability index and cognitive failures was used to collect data. The data were analyzed using SPSS 20 and the Pearson and Spearman correlation coefficients, chi-squared, ANOVA, and the Kruskal-Wallis tests.Using the Pearson correlation test, the results of this study showed that there is a significant, inverse relationship between WAI, personal prognosis of work ability, and mental resources with CFs along with all its subscales in nurses (p < 0.05). In addition, there was an inverse and significant relationship between the total score of CFs and the estimated work impairment due to diseases (p < 0.05). There was a significant positive correlation of CFs with age and experience, while WAI was inversely related to age, work experience, and body mass index (BMI) (p < 0.05). WAI and CFs were related significantly to working units (p < 0.05).Considering the results obtained in this study, WAI and the cognitive status of nurses were lower than the specified limit. It is suggested that the work ability of nurses be improved and that their CFs be reduced through various measures, including pre-employment examinations, proper management of work-shift conditions, and using engineering and administrative strategies to ensure the safety of hospitalized patients.