Background: Antibiotic resistance is now considered as a global problem. Due to the increasing use of antibiotics, and subsequent increase in antibiotic resistance, treatment of bacterial infections has faced many difficulties. Objectives: This study aimed to investigate the pattern of antibiotic resistance in Escherichia coli (E. coli) isolated from patients referred to the hospital during the years 2016-2018. Methods: In this cross-sectional study, 2250 samples were taken from outpatient and hospitalized patients (inpatients) during three years (2016-2018). After collection, the specimens were cultured in blood agar and EMB media. One thousand six hundred and fortytwo positive samples were obtained that from these, a number of 1067 specimens were recognized as E. coli. Antibiotic susceptibility was determined using a disk diffusion method on Mueller Hinton agar media for eight antibiotics. The result was evaluated based on the Clinical Laboratory Standards Institute (CLSI). Results: In this study, 1642 positive samples were diagnosed that the largest isolated strains were associated with E. coli (65%). About 241 samples belonged to men (22.6%) and 826 samples were isolated from women (77.4%). Based on the findings, most cases of resistance were related to co-trimoxazole with 52.6% and the highest sensitivity was related to nitrofurantoin with 81%. Conclusions: The results of this study indicated that the pattern of antimicrobial resistance is increasing and urinary tract infection (UTI) caused by E. coli isolates with a high rate of resistance still remains an important healthcare problem. Therefore, continuous evaluation of the pattern of resistance in different areas is necessary for promotion of antibacterial management.