Significant increases in antibiotic resistance have become a critical dilemma in healthcare systems around the world. Enterobacteriaceae acquired different mechanisms of antibiotic resistance such as ESBLs production and transposon attainment, which hold antibiotic resistance genes. This may create multidrug resistant (MDR) strains. Antibiotic resistance patterns vary in different geographical regions. The present estimated-cross sectional study is aimed to determine antibiotic resistance pattern of 182 E. coli strains to 20 antibiotics. Three different methods were applied to detect the ESBL-producing E. coli. Observations revealed that oxacillin, amoxicillin and ampicillin had the lowest effect, while imipenem, gentamicin and nitrofurantoin had the highest impact on clinical E. coli strains in our region. Three different methods, including double disk synergy test (DDST) (30 mm), double disk synergy test (DDST) (20mm) and combined disk test were used to identify ESBL-producing E. coli. The prevalence of ESBL producers was at a 35.71% rate. Findings of this study indicate that there is no significant difference between these three methods in identifying ESBLproducing E. coli. There was a significant relation between ESBL production and resistance to three other classes of antibiotics, including protein synthesis inhibitor, Quinolones and Metabolite analogues. Moreover, antibiotic resistance rate in ESBL-producing E. coli was significantly higher than non ESBL- producing isolates. The MDR was at a 65.93% rate. Unfortunately, the rate of antibiotic resistance is globally increasing; this is due to several factors such as inappropriate antibiotic use, incomplete course of antibiotics use, protracted length of stay in hospitals and self-medication. Resistance mechanisms such as ESBL production and MDR cause treatment failure. Our findings suggest that ESBL production is a risk factor for MDR in clinical E. coli. Therefore, Physicians are recommended to stop excessive and long term administration of antibiotics.