INTRODUCTION Universal precautions include a group of infection prevention practices that apply to all patients, regardless of suspected or confirmed infection status, in any setting in which healthcare is delivered. The group of practices includes Barrier precautions, Hand hygiene, careful handling and disposal of sharp medical instruments. AIM & OBJECTIVES The study was conducted with the aim to assess the knowledge of Universal safe precautions and the compliance with Universal safe precautions among nurses of tertiary care multispecialty hospital in Delhi and further to suggest actions for improvements. MATERIAL AND METHOD This cross sectional observational study was conducted in February to April 2018 in tertiary care multispecialty hospital in Delhi. A total of 40 participants were drawn from the total population using randomization method. A structured questionnaire was designed. It included three parts; socio–demographic data, 15 questions to assess the level of knowledge and 20 questions designed to collect information about the compliance of nurses towards Universal Precautions. For data analysis, descriptive statistics in the form of frequencies and percentages was used. RESULTS All the participants were females with mean age of 29.05 yrs and with mean of 6.24 years of work experience. Among all, only 4 nurses had average knowledge score i.e. < 80%, 31 nurses had good knowledge i.e. 80–87% and only 5 had very good knowledge score i.e. > 90%. So, majority of nurses, 77.5 % attained good knowledge score. It was observed that all of them were aware of Universal precautions but had very sparse knowledge about the main objective of the UPs i.e only 12.5% nurses were aware of the objectives of UPs. 12.5% participants were in favour of wrong statement ‘Universal Precautions should only be used in patients diagnosed with infection or patients who are in the incubation period for a given infection’. The data stated that all of them were well versed with the protocol of hand washing, use of gloves, usage of PPE and precautions to be taken while providing care to patients of tuberculosis, chicken pox, intestinal and skin infections. It was observed that the compliance rate was very low during giving injections i.e. 55% only. Use of protection apron, caps, and shoe covers was also not meticulously being followed by all; the compliance rate was between 65–70%. It was also observed that only 10% of the study population were aware of the precautions to be taken after workplace accidents with potentially contaminated sharp materials. For rest of variables, compliance to UPs was satisfactory among nurses. CONCLUSION There was adequate knowledge and a fair level of compliance among nurses towards Universal Precautions. Specific training programs may have to target health care workers to establish acceptance of appropriate practices that will enable them to better adopt and adhere to universal precautions.