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Background Focal segmental glomerulosclerosis (FSGS) is characterized by the presence of glomerular damage on histopathological examination. The major defining symptom of FSGS is proteinuria, which indicates damage to the glomerular filtration barrier. Additionally, FSGS is the most common cause of primary nephrotic syndrome. However, in Saudi Arabia, there is a paucity of research on this topic. Therefore, this study was designed to examine the clinical features, laboratory findings, and presence of comorbidities in patients with FSGS to determine their effects on clinical outcomes. Methods We retrospectively analyzed the histopathological and clinical data of patients diagnosed with FSGS via biopsy at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, during the period 1989-2020. Biopsy samples were labeled according to the Columbia classification as tip, perihilar, cellular, collapsing, or not otherwise specified (NOS). Results We included 39 children and 21 adults. Males accounted for 54.1% of the sample. Hypertension was the most common comorbidity. Regarding FSGS subtypes, 60.9% of the lesions in the adult patients were collapsing lesions, followed by NOS (26.1%). In pediatric patients, 36.8% of the lesions were NOS, followed by collapsing lesions (28.9%). We also observed a very low rate of remission. In both age groups, the most common clinical presentation was nephrotic syndrome. Conclusion We found a high prevalence of collapsing and NOS FSGS subtypes in both the adult and pediatric age groups. The most prevalent outcome was the persistence of nephrotic syndrome with low rates of remission., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Alhozali et al.)