Focal segmental glomerulosclerosis (FSGS) can lead to kidney failure in adults. This study examines the progression of FSGS in the German Chronic Kidney Disease (GCKD) cohort. The GCKD study (N=5217), a prospective cohort, included 159 patients with biopsy-confirmed FSGS recruited from 2010 to 2012. Baseline was defined as the first study visit. Adjudicated endpoints included a composite kidney endpoint (CKE), including an estimated glomerular filtration rate (eGFR) decrease >40%, eGFR <15ml/min/1.73m2 or initiation of kidney replacement therapy and combined major adverse cardiovascular events (MACE), including non-fatal myocardial infarction or stroke and all-cause mortality. Associations between baseline demographics, laboratory data, comorbidity and CKE and MACE were analysed using the Cox proportional hazards regression model. The mean age at baseline was 52.1±13.6years, with a disease duration of 4.72years (quartile 1: 1; quartile 3: 6) before joining the study. The median urinary albumin:creatinine ratio (UACR) at baseline was 0.7g/g (IQR 0.1;1.8), while mean eGFR was 55.8±23ml/min/1.73m2. Based on clinical and pathological features, 69 (43.4%) patients were categorized as primary FSGS, 55 (34.6%) as secondary FSGS and 35 (22%) as indeterminate. Over a follow-up of 6.5years, 44 patients reached the composite kidney endpoint and 16 individuals had at least one MACE. UACR ≥0.7g/g was strongly associated with both the composite kidney endpoint {hazard ratio [HR] 5.27 [95% confidence interval (CI) 2.4-11.5]} and MACE [HR 3.37 (95% CI 1.05-10.82)] compared with <0.7g/g, whereas a higher eGFR at baseline (per 10ml/min) was protective for both endpoints [HR 0.8 (95% CI 0.68-0.95) and HR 0.63 (95% CI 0.46-0.88), respectively]. Patients with secondary FSGS experienced a greater rate of eGFR decline than patients with primary FSGS. Lower eGFR and higher albuminuria are key risk factors for kidney disease progression and cardiovascular events in patients with FSGS.