Focal periphyseal edema (FOPE) zones were first described in 2011. The aim of this report was to investigate the clinical course of patients with FOPE zones. Three adolescent patients with a FOPE zone in the knee were treated and observed for a maximum of 2 years. No symptoms or leg-length discrepancy developed at the final follow-up after conservative therapies. This is the first report on the follow-up of FOPE zones with a maximum of 2 years. The results suggest that observation of FOPE zones may be sufficient without invasive examinations and treatment.