Background: arterial lines are used to obtain precise measurement and provide continuous blood pressure monitoring of critically ill patients. Critical care nurses are the primary responsible clinician for maintaining the safety and effectiveness of arterial lines. Aim: Assess nurses' compliance with safety measures of arterial line. Research Design A descriptive exploratory design was utilized to meet the aim of this study and to answer the research question. Setting: This study was conducted in three ICU units at Academy of Heart which affiliated to Ain shams University Hospitals. Tools:  Two tools used Nurses' Self-administered questionnaire, and Practice compliance–related safety measures observational checklist. Results: revealed that, 75.0% of the studied nurses aged 18-30 years with mean age (28.83 ± 7.459) years, 80.4% hadn't training in safety measures in arterial line, and 80.3% had unsatisfactory total level of knowledge & incompetent total level of practice. Moreover, 76.3% of studied nurses reported that total factors affect their compliance with safety measure in arterial catheter. Additionally, there was a statistically significant correlation between studied nurses' total knowledge about safety measures in arterial line and their total compliance and factors affecting their compliance. Conclusion: A majority of the study nurses had an unsatisfactory level of knowledge & incompetent level of practice in following arterial line safety measures. Additionally, a substantial number of the study nurses recognize that certain factors impact their ability to comply with safety measures of arterial line. Recommendations: Replication of the current study on large sample and different hospitals settings to generalize the results.