Introduction: Medication errors are the number-first error in health care (Centres for Disease Control [CDC], 2013). Safe and right medication administration is a major and potentially challenging nursing responsibility. Medication administration requires fine decision-making skills and clinical judgment hence, the nurse is accountable for ensuring full apprehension of medication administration and its involvement for patient safety. Aim: The aim of study was to assess the knowledge regarding safe medication administration among staff nurses of Pediatrics department in Government Medical College, Amritsar, Punjab. Materials and methods: A quantitative research approach with a descriptive research design was selected for the study. Total sampling was done on 100 among staff nurses of Pediatrics department in Government Medical College, Amritsar, Punjab. A structured Questionnaire containing 30 multiple choice items were used to assess the knowledge regarding safe medication administration among staff nurses of Pediatrics department in Government Medical College, Amritsar, Punjab. Both descriptive and inferential statistical methods were used for the analysis of data. Chi-square test was applied to find out the association between knowledge of staff nurses of Pediatrics department in Government Medical College, Amritsar, Punjab. with selected variables. Results: The results of the present study revealed that the majority of staff nurses of Pediatrics department in Government Medical College, Amritsar, Punjab. have adequate knowledge i.e. 70%. and 23% have moderate knowledge, on the other hand 7% have inadequate knowledge There is a significant relationship of knowledge with demographic variables i.e. age (x2=16.351, p=0.00), education (x2=15.364, p=0.004) and no. of staffs working in the ward (x2=13.738, p=0.008), no. of patient ratio in the ward ((x2=9.329, p=0.049) found statistically significant at 0.05 level. Whereas others gender, working unit, and no. of patients in the ward found non-significant at 0.05 level. Conclusion: It is concluded that there was the majority of staff nurses of Pediatrics department in Government Medical College, Amritsar, Punjab. have adequate knowledge i.e. 70%. and 23% have moderate knowledge, on the other hand 7% have inadequate knowledge inadequate knowledge. and there should be informational booklet to enhance the knowledge of staff nurses of Pediatrics department in Government Medical College, Amritsar, Punjab.