Background: Statin monotherapy is a cornerstone of lipid-lowering therapy for reducing low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk in patients with dyslipidemia. However, many patients at moderate-to-high cardiovascular risk fail to achieve recommended LDL-C targets with statin therapy alone, prompting interest in combination lipid-lowering strategies. Ezetimibe inhibits intestinal cholesterol absorption through Niemann–Pick C1-like 1 (NPC1L1) protein inhibition and may enhance LDL-C reduction while allowing lower statin doses, potentially improving tolerability. Objective: To compare the efficacy and short-term safety of moderate-intensity rosuvastatin (10 mg) combined with ezetimibe (10 mg) versus high-intensity rosuvastatin (20 mg) monotherapy in patients with dyslipidemia. Methods: This prospective randomized controlled study included 60 patients who completed 24 weeks of follow-up after random allocation to either rosuvastatin/ezetimibe (10/10 mg) combination therapy or rosuvastatin 20 mg monotherapy. Lipid profile, liver enzymes (AST and ALT), and creatine kinase (CK) were measured at baseline and at week 24. Continuous variables were analyzed using repeated-measures general linear modeling and mixed-model ANOVA after assessment of data normality. Safety evaluation included biochemical monitoring and clinical assessment for adverse events. Results: Both treatment groups demonstrated significant reductions in total cholesterol and LDL-C from baseline (both p < 0.001). Post-treatment LDL-C was significantly lower in the combination group than in the monotherapy group (71.83 ± 12.14 vs. 86.30 ± 23.87 mg/dL; p = 0.004), whereas reductions in total cholesterol, triglycerides, and HDL-C changes were comparable between groups. Absolute post-treatment AST and ALT values did not differ significantly between treatment groups. However, percentage increases from baseline were significantly smaller in the combination group for AST (15.38% vs. 35.71%; p = 0.015) and ALT (14.28% vs. 21.11%; p = 0.018). Importantly, mean liver enzyme values in both groups remained well below clinically significant hepatotoxicity thresholds throughout follow-up. No major adverse cardiovascular events occurred during the 24-week study period. Conclusions: Moderate-intensity rosuvastatin combined with ezetimibe achieved lipid-lowering efficacy comparable to high-intensity rosuvastatin while producing lower relative increases in liver enzymes over 24 weeks. These findings suggest that combination therapy represents a reasonable therapeutic alternative for selected patients requiring intensive LDL-C reduction; however, larger multicenter studies with longer follow-up are needed to establish comparative cardiovascular outcomes and overall safety. Clinical trials: https://clinicaltrials.gov/study/NCT07313124 .