Background The global burden of infections due to multidrug-resistant organism (MDRO) has a significant impact on patients' morbidity and mortality along with increased healthcare expenditure. Aim This article estimates the prevalence of MDRO and the spectrum of clinical infectious syndromes caused by these organisms in medical wards of a tertiary care hospital in India. Design and Methods A cross-sectional observational study was performed among patients admitted in medicine wards diagnosed with the various infectious syndromes and one or more clinically significant positive culture at a tertiary care hospital in North India over a period of 18 months. Results Out of 323 clinically significant microbiological culture isolates from 229 patients included in the study, 86 (27%) isolates showed multidrug resistance (MDR) pattern, 197 (61%) isolates showed possible extremely drug-resistance pattern, and only 40 (12%) isolates showed nonmultidrug-resistance pattern of antibiogram. Conclusion The prevalence of MRDOs is high in clinically significant culture isolates from medicine wards in India. This emphasizes the importance of appropriate antibiotic usage and implementation of antibiotic stewardship programs in this part of the world., Competing Interests: Conflict of Interest None declared., (The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.).)