Background: Antibiotic prescription trends analysis is essential for monitoring the sensitivity and resistance patterns of microorganisms discovered, regularly generating and updating antibiograms, and providing the context for antibiotic usage and prevalence. Specifically, consistent prescription patterns and antibiotic therapy practices with the WHO AWaRe (Access, Watch, and Reserve) classification of antibiotics and the national or WHO essential medicine list would enhance the prudent use of antibiotics, prevent the emergence and spread of antimicrobial resistance, and preserve antibiotic efficacy for future requirements. Objective: This study aimed to analyze selection of antibiotics for empirical use and definitive therapy and to evaluate rational use of antibiotics according to the WHO-AWaRe (Access, Watch, and Reserve) categories in hospitalized patients. Methodology: An observational and cross-sectional study was conducted in a 300 bedded multispecialty tertiary care hospital from October 2022 to March 2023 for a period of six months. Evaluation of demographic data based on antimicrobial susceptibility reports, pathogen characteristics, and infection site; evaluation of antibiotics administered before and after AST reports; and classification of antibiotics using WHO AWaRe metrics from the WHO essential medicines list. Descriptive statistics were applied for the data collected using Microsoft Excel. Results are expressed as total count, frequency, and percentages. Results: Antimicrobial susceptibility results from 162 patients were gathered from the laboratory. Of these 138 (85.18%) patients had positive results for Gram-negative bacteria and 24 (14.81%) for Gram-positive bacteria. The mean (SD) age of patients was 55 ± 28 years; predominantly male patients 92 (56.79%). 107 (66%) patients were hospitalized for 1-5 days. Monotherapy was given in 17 (10.5%) patients, Most of the patients were admitted into the general medicine 94 (58.02%), Bacteria were mainly isolated from urine (65 isolates, 40.1%), and a total of 36 organisms were isolated. The proportions of appropriate empirical therapy use were 84.05% for Gram-negative bacteria. A total of 706 antibiotics were prescribed out of which 334 are prescribed before AST and 372 are prescribed after AST. More prescribed empirical antibiotics were from the ‘Watch’ group (55.69%), followed by the ‘Access’ group (25.75%). ‘Reserve’ category (8.38%) and ‘not-recommended’ category (10.18%) antibiotics were also prescribed. A greater number of prescribed definitive antibiotics were from the ‘Watch’ group (48.11%). ‘Access’ group antibiotics should be preferable to the ‘Watch’ group. ‘Reserve’ antibiotics are always used as the last option when “Access” and “Watch” group antibiotics don’t work. Conclusion: The high use of empirical antibiotics especially from the ‘Watch’ category is a disturbing trend as observed in our study. . Increasing the use of ‘Access' antibiotics while limiting the use of ‘Watch' and ‘Reserve' antibiotics at the same time is the highest priority for preserving effectiveness of important antibiotics and minimizing the danger of AMR. Conducting such studies and analysis of such data periodically would pave the way for promotion of rational use of antimicrobials and help restrict the emergence of resistant strains of bacteria.