(1) Background: Bacterial infections are frequently encountered in liver cirrhosis and may be associated with a dismal prognosis. Over recent decades, antibiotic resistance has increased, which may be linked to higher mortality. (2) Methods: We conducted a retrospective study between 2018 and 2024, evaluating all patients with cirrhosis and ascites admitted to our hospital. Antimicrobial susceptibility testing was performed on all bacterial isolates. Multivariate analysis was used to identify predictive risk factors for in-hospital death. (3) Results: In total, 806 patients were identified during the study period; 78 had spontaneous bacterial peritonitis (SBP), 6 had bacterascites, 74 had Clostridioides difficile infection (CDI), 27 had culture-positive pneumonia, 24 had urinary tract infection, and 20 had bloodstream infection (BSI). Antibiotic resistance rates were high, with multidrug-resistant (MDR) strains detected in 70.3% of cases. The isolated pathogens included MRSA (65.9%), ESBL-producing Gram-negative bacilli (18.5%), and carbapenem-resistant Gram-negative strains (31.1%); only one case of vancomycin-resistant Enterococcus (VRE) was recorded. In multivariate analysis, liver disease severity; AKI and ACLF presence; multiple infection sites; and culture-positive pneumonia, BSI, and SBP were associated with higher mortality. Gram-negative infections were also associated with higher mortality rates. (4) Conclusions: In total, 22.1% of patients hospitalised with cirrhosis and ascites had at least one confirmed bacterial infection. Increased antibiotic resistance and a high proportion of MDR were recorded. The severity of liver disease, AKI and ACLF presence, the presence of pneumonia, BSI, and SBP, Gram-negative and multiple infection sites were associated with higher mortality.