Aims and Objectives: Aim of the study is to estimate prevalence of Escherichia coli among clinically suspected Urinary Tract Infection cases and comparison of antibiogram between Nitrofurantoin VS Fosfomycin as the first line agent for treatment of Urinary Tract Infection caused by Escherichia coli. Materials and Methods: The study was conducted on urine samples over a period of six months (August 2022 to January 2023) during which 3215 urine samples were taken from patients at King George Hospital, Visakhapatnam and were processed for bacterial culture and sensitivity. Out of 3215 urine samples,816 were culture positives among them, 373 were Escherichia coli isolates and these isolates were subjected to Antibiotic susceptibility by Kirby-Bauer disc diffusion Method according to the Clinical Laboratory Standard Institute Guidelines 2022 in Microbiology department, Andhra Medical College. Results: Among 816 culture positives, 373 isolates were Escherichia coli (45.71%), followed by Klebsiella sps (26.5%), others were Acinetobacter sps, Candida sps, Pseudomonas sps, Proteus sps, Enterococcus sps, Citrobacter sps and MRSA. The Antibiotic susceptibility of Escherichia coli isolates to Nitrofurantoin and Fosfomycin was 89.54% and 73.99% respectively. Conclusion: This study helps us to understand that Escherichia coli is the common Urinary pathogen causing Urinary Tract Infection. The use of Nitrofurantoin and Fosfomycin against Escherichia coli indicates that these two drugs are therapeutic alternatives for Urinary Tract Infection. Among these two drugs, Nitrofurantoin is most effective in the empirical treatment of Urinary Tract Infections.