Nurses are faced with professional hazards such as needle pricks and blood-borne infections in their day to day activities in the work place. This study is aimed at finding out the knowledge and practice of universal precautions among nurses at the Central Hospital, Benin City, Edo State, Nigeria. One hundred and fifty-five (155) nurses participated in the cross-sectional study. The nurses were selected using the stratified random sampling method. The nurses had a poor knowledge about universal precautions as only 34.2% of nurses had heard about universal precautions. There was also a poor observance of universal precautions. Knowledge of measures to be taken after the occurrence of occupational accidents/ injuries was also poor, as only 26(16.8%) nurses would report puncture injuries to the clinic, only 13(8.4%) nurses would screen patients for HIV antibody after consent when they sustain work related accident/injuries. Twelve (7.7%) nurses would screen patient to determine hepatitis B status of patient while only 8(5.2%) nurses would go for medical check-up/immunisation with hepatitis B vaccine.