Considering urinary tract infections (UTIs), a significant public health problem with negligible recent research, especially on the male eastern European population, we aimed to determine the antimicrobial resistance rates of uropathogens for the most commonly used antibiotics in urological practice in our country. We conducted a multicenter retrospective study in two different teaching hospitals in Romania, analyzing urine samples from 7719 patients to determine the frequency of incriminating pathogens and their resistance to different antibiotics, in a comparative approach. We determined Escherichia coli (35.98%) to be the most common pathogen with the highest sensitivity to amikacin (S = 91.72%), meropenem (S = 97.17%) and fosfomycin (S = 86.60%) and important resistance to amoxicillin-clavulanic ac. (R = 28.03%) and levofloxacin (R = 37.69%), followed by Klebsiella spp. (22.98%) with the highest sensitivity to amikacin (S = 78.04%) and meropenem (S = 81.35%) and important resistance to amoxicillin-clavulanic ac. (R = 65.58%) and levofloxacin (R = 45.36%); the most frequent Gram-positive pathogen was Enterococcus spp. (19.73%) with the highest sensitivity for vancomycin (S = 93.75%) and fosfomycin (S = 87.5%) and considerable resistance to penicillin (R = 33.52%) and levofloxacin (R = 42.04%). The findings are an important tool in managing UTIs and should be acknowledged as reference research not only for clinicians from Romania but for all physicians treating male UTIs.