Objectives: In resource limited countries facing a huge burden of multidrug resistant and extensively drug resistant (XDR) enteric fever, treatment is a great challenge on the part of a patient as well as a health care professional. This study was conducted to determine the association of XDR enteric fever with various studied factors among hospitalized culture-positive pediatric patients in a tertiary care hospital setup. Methods: We conducted a descriptive observational study at The Karachi Adventist Hospital from July 01, 2019, to March 31, 2020 on 143 hospitalized children with culture proven enteric fever who were already on empirical antibiotics. Depending on the variability of the course of illness and clinical responses to given antibiotics, the data was gathered on a structured data sheet. Association of various study parameters and their significance in relation to XDR salmonella infection was analyzed and studied. Results: The age group highly affected was 5-7.5 years, with a male preponderance of 61.5%. Majority were from urban slums areas of Karachi (53.8%) and 52% were admitted between 7 to 14 days of fever onset. XDR salmonella infection was observed in 79% of blood culture isolates. None of the XDR patients were consuming boiled water and neither of these infected children were vaccinated against salmonella typhi. Duration of fever before hospitalization, non-consumption of boiled or mineral water, ciprofloxacin use and lack of typhoid vaccination showed statistically strong association with XDR enteric fever (p<0.01). Conclusion: Prehospitalization fever duration, use of boiled/mineral water, ciprofloxacin use and typhoid vaccine status showed strong association with XDR salmonella infection. Prioritizing the focus on healthcare awareness, early access to proper health care facility, discouraging over-the-counter drugs and enforcement of immunization will help decline the dissemination of this dreadful disease. doi: https://doi.org/10.12669/pjms.38.7.5868 How to cite this:Memon H, Saeed F, Iqbal M, Saboohi E, Hanif S, Mallick AHH. Association of extensively drug resistant salmonella infection in children with typhoid fever. Pak J Med Sci. 2022;38(7):---------. doi: https://doi.org/10.12669/pjms.38.7.5868 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.