Background and objectives: We conducted a meta-analysis to evaluate the comparative efficacy of hypertonic saline (HS) versus mannitol in the management of elevated Intracranial Pressure (ICP) among patients with Traumatic Brain Injury (TBI). Materials and methods: A systematic literature search up to February 2025 identified 18 studies including 1,828 patients with TBI. The analysis compared the effects of HS and mannitol on elevated ICP control. Odds Ratios (ORs) and Mean Differences (MDs) with 95% Confidence Intervals (CIs) were calculated using dichotomous or continuous approaches, applying either fixed- or random-effects models. Results: Compared with mannitol, HS was associated with a significantly lower treatment failure rate (OR 0.38; 95% CI 0.15-0.98; p=0.04), higher cerebral perfusion pressure at 30-60 minutes post-infusion (MD 5.25; 95% CI 3.59-6.91; p<0.001), and lower ICP at 30- 60 minutes (MD-1.12; 95% CI -2.11 to -0.12; p=0.03). However, HS did not significantly affect mortality, functional outcomes, cerebral perfusion pressure at 90-120 minutes, ICP at 90-120 minutes, or the daily duration of elevated ICP. Conclusion: In patients with TBI, HS was superior to mannitol in reducing treatment failure, improving cerebral perfusion pressure, and lowering ICP within 30-60 minutes of administration. However, no significant differences were observed in mortality, long-term functional outcomes, or ICP control beyond 90 minutes. These findings suggest HS may offer short-term hemodynamic advantages over mannitol, but larger, high-quality trials are required to confirm its long-term clinical benefit.