<p>The aim of this study is to analyze data from all cases of Susac syndrome that have been published in the literature. This study was conducted in conformity with the PRISMA statement. A systematic review and survival analysis was performed for overall survival (OS) and progression-free survival (PFS). A total of 435 patients (males: 32.6%, <i>n</i> = 142), derived from 176 studies, were included in the analysis. The median age at diagnosis was 35&#xa0;years (<i>n</i> = 433/435; range 7–69). Neurological symptoms were the most frequent (87.4%, <i>n</i> = 380/435). Among audio-vestibular symptoms (84.3%, <i>n</i> = 365/433), hearing loss was the most common manifestation (87.9%, <i>n</i> = 327/372). Branch retinal artery occlusions (BRAOs) were observed in 91.6% of patients (<i>n</i> = 261/285), while ophthalmological symptoms were reported in 78.9% (<i>n</i> = 288/365). The complete triad at onset was present in only 20.1% (<i>n</i> = 61/304) of cases. Complete recovery without sequelae was achieved in 59.5% (<i>n</i> = 44/74) of patients which reported neurological involvement, 39.7% (<i>n</i> = 27/68) of those with ophthalmological symptoms, and 17.7% (<i>n</i> = 11/62) of those with audio-vestibular symptoms. Partial recovery was observed in 36.5% (<i>n</i> = 27/74), 50.0% (<i>n</i> = 34/68), and 38.7% (<i>n</i> = 24/62) of patients, respectively. In a subgroup of 123 patients with available follow-up data (median duration: 12&#xa0;months), 82.1% (<i>n</i> = 101) remained stable with controlled disease, 12.2% (<i>n</i> = 15) experienced a relapse, and 5.7% (<i>n</i> = 7) died. OS at 1 and 3&#xa0;years was 94% (95% CI 88–97%). PFS was 89% at 1&#xa0;year (95% CI: 80–94%) and 83% at 3&#xa0;years (95% CI: 69–91%). Susac syndrome presents a significant clinical challenge. While presentations and outcomes are very heterogeneous, mortality is uncommon. The potential for relapse and long-term sequelae highlights the need for greater awareness and deeper understanding of the disease.</p>