Background: Urinary tract infection (UTI) is caused by the colonization and multiplication of pathogenes in the urinary tract. Patients with diabetes mellitus (DM) have weakened host defense, making them more vulnerable to UTI. Overuse of antibiotics frequently causes pathogens associated with UTI to become more resistant to the most commonly used antimicrobials.This calls for ongoing monitoring of the uropathogens and antibiogram to better patient care. Objective: This study was aimed to determine the prevalence of urinary tract infections, antimicrobial susceptibility profiles and factors associated with UTI among DM patients. Methods: A hospital-based cross-sectional study was conducted at Debre Tabor Comprehensive Specialized Hospital (DTCSH) from 15 May 2022 to 13 July 2022. Structured questionnaire was used to collect socio-demographic characteristics and clinical information of the study participants. Urine samples were collected following standard bacteriological procedures. MacConkey agar, blood agar, manitol salt agar, and bile esculin agar were used for bacterial isolation and characterization. Muller Hinton agar was used for antimicrobial susceptibility testing following the disck diffusion technique. Data were entered and analyzed using SPSS version 25. Descriptive statistics were used to present the findings. Logistic regression analysis was performed to identify factors associated with UTI among DM patients. Statistical significance was set at p- value <0.05. Results: In this study, 246 study participants were included. The prevalence of significant bacteriuria (SBU) among DM patients was 35 (14.2%). Twenty-five of the 35 positive cases (71.4%) were females. Of the 35 isolates, 29 (82.9%) were gram-negative and the remaning were gram-positive. The predominate isolates were E. coli 18 (51.4%), Klebsiella ozaenae 6 (17.1%), S. aureus 5 (14.3%), and K. pneumoniae 3 (8.6%). Gram- negative isolates were found to be resistant to amoxicillin, co-trimoxazole, and cefotaxime at 57.1%, 39.3%, and 35.7% rate, respectively. On the other hand, these isolates were found sensitive to nitrofurantoin (96.4%), gentamycin, ciprofloxacin, and impenem each at 89.7%. The proportion of antibiotic resistance among gram-positives ranged 33.3% to 100%.The overall multi-drug resistance (MDR) rate was 54.3%. Patients with UTI symptoms (p=0.002) and sex being female (p=0.048) were found to be important factors associated with SBU among DM patients. Conclusion: A higher prevalence of SBU was documented among DM patients in the study area. Gram negative islates that were resistant for commonly used antimicrobials were dominant. Therfore, actions to minimize antimicrobial resistance should be strengthened. Keywords: Urinary tract infection, diabetes mellitus patients, antimicrobial susceptibility, bacteria, Debre Tabor