Purpose: Childhood cancer survivors are at high risk of late adverse effects of cancer treatment, but there are still many gaps in evidence about these late effects. We described the methodology, clinical characteristics, data availability, and outcomes of our cohort study of childhood cancer survivors. Methods: The Emma Children's Hospital/Academic Medical Center (EKZ/AMC) childhood cancer survivor cohort is an ongoing single-center cohort study of ≥5-year childhood cancer survivors, which started in 1996 simultaneously with regular structured medical outcome assessments at our outpatient clinic. Results: From 1966 to 2003, 3,183 eligible children received primary cancer treatment in the EKZ/AMC, of which 1,822 (57.2 %) survived ≥5 years since diagnosis. Follow-up time ranged from 5.0 to 42.5 years (median, 17.7). Baseline primary cancer treatment characteristics were complete for 1,781 (97.7 %) survivors, and 1,452 (79.7 %) survivors visited our outpatient clinic. Baseline characteristics of survivors who visited the clinic did not differ from those without follow-up. Within our cohort, 54 studies have been conducted studying a wide range of late treatment-related effects. Conclusions: The EKZ/AMC childhood cancer survivor cohort provides a strong structure for ongoing research on the late effects of childhood cancer treatment and will continuously contribute in reducing evidence gaps concerning risks and risk groups within this vulnerable population. Implications for Cancer Survivors: Our large cohort study of childhood cancer survivors with complete baseline characteristics and unique, long-term medical follow-up decreases gaps in evidence about specific risks of late effects and high-risk groups, with the ultimate goal of improving the quality of care for childhood cancer survivors.