Background: Cirrhosis predisposes patients to focal liver lesions (FLLs), including benign nodules and hepatocellular carcinoma (HCC), necessitating early and accurate imaging for timely diagnosis and management. Contrast-enhanced computed tomography (CECT) is widely used for liver lesion characterization, but contrast-enhanced ultrasound (CEUS) has gained attention as a real-time, radiation-free alternative with superior vascular assessment. This study compares CEUS and CECT in diagnosing focal liver lesions in cirrhotic patients, assessing their diagnostic accuracy, sensitivity, and clinical utility. Objectives: To compare the efficacy, diagnostic accuracy, and limitations of CEUS and CECT in characterizing focal liver lesions in cirrhotic patients, differentiating benign from malignant lesions, and evaluating their clinical role in liver lesion detection and staging. Methods: A prospective comparative study was conducted on 120 cirrhotic patients with suspected focal liver lesions at a tertiary care center. All patients underwent both CEUS and CECT within one week for lesion characterization based on vascular phases, washout kinetics, and enhancement patterns. Lesion classification was compared with histopathology, MRI confirmation, or follow-up imaging over six months. Statistical analysis included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy for both imaging modalities, using receiver operating characteristic (ROC) curves and McNemar’s test. Result: Among 120 patients, 80 (66.7%) had malignant lesions (HCC, cholangiocarcinoma, metastases) and 40 (33.3%) had benign lesions (regenerative nodules, hemangiomas, focal nodular hyperplasia). CEUS demonstrated a sensitivity of 91.2%, specificity of 87.5%, and overall accuracy of 89.6%, while CECT showed a sensitivity of 94.6%, specificity of 83.3%, and accuracy of 90.8%. CEUS outperformed CECT in characterizing small lesions (<2 cm) and detecting arterial phase hyperenhancement, while CT was superior in identifying multifocal lesions, extrahepatic spread, and portal vein thrombosis. The concordance rate between CEUS and CECT was 88.4%, with CEUS misclassifying 8 cases and CECT misclassifying 10 cases due to overlapping enhancement patterns and lesion heterogeneity. Conclusion: Both CEUS and CECT exhibit high diagnostic accuracy in differentiating benign and malignant focal liver lesions in cirrhotic patients. CEUS excels in real-time vascular assessment and detecting early arterial-phase enhancement, particularly in small lesions, while CECT remains superior for staging, detecting multifocal disease, and assessing extrahepatic involvement. A combined imaging approach may enhance diagnostic precision, especially for indeterminate lesions or high-risk cirrhotic patients. Future research should explore the integration of CEUS in routine liver imaging protocols and its cost-effectiveness in cirrhosis-related lesion detection.