Medications administration through enteral feeding tube seems to be a challenge, if medications are not given appropriately through the enteral route, it may result in harmful consequences. Aim: The aim of this study was to evaluate the influence of intervention guidelines on nurses' knowledge and skills about medication administration by enteral feeding tube. Research hypotheses: The current study hypothesized that: Implementing guidelines intervention about medication administration by enteral feeding tube will affect nurses' knowledge and skills positively. Design: A quasi experimental design (one group pretest- posttest) was utilized in this study. Subjects: A convenient sample of all available nurses (50 nurses). Setting: The study was conducted at medical and surgical intensive care units at Kafr Elsheikh University hospital. Tools: Two tools were used, a nurses' knowledge assessment questionnaire and nurses' observational checklist. Results: the result showed that mean age of studied nurses was 31.82±7.61. While, 62% of them were males, and 86% had bachelor degree in nursing. The study revealed that 100% of the studied nurses had a satisfactory level of knowledge about medication administration by enteral feeding tube post implementation of intervention guidelines and 84% of the studied nurses had a satisfactory level of skills about medication administration by enteral feeding tube post guidelines implementation. Conclusion: Based on the results of the present study, it can be concluded that implementing intervention guidelines about medication administration by enteral feeding tube had a positive effect on nurses' knowledge and skills. There was a statistically significant difference between nurses' knowledge and skills post guidelines intervention at p≤ 0.001. Recommendations: Continuous training programs for nurses to improve and update nurses' knowledge and skills about safe administration of medication by enteral feeding tube, Provision of nurses with simple illustrated booklet and posters about medications administration by enteral route and food-drugs interactions, and further studies should be carried out in different settings on a larger sample to be able to generalize the results.