Objectives: The aim of this study is to evaluate neurodevelopmental and cognitive outcomes in patients diagnosed with different types of hyperphenylalaninemia (HPA), identify the factors influencing these outcomes, and contribute to the debate regarding the thresold for initiating dietary treatment based on plasma phenylalanine (Phe) levels. Methods: Patients with hyperphenylalaninemia (HPA) who were followed up and had developmental and/or cognitive evaluations at the Division of Pediatric Metabolism and Nutrition, Department of Pediatrics, between 1984 and 2018, were retrospectively assessed. Results: A total of 342 patients were included in the study, comprising 182 (53.2%) females and 160 (46.8%) males. Conclusion: In addition to early diagnosis and treatment, lifelong adherence and regular follow-up are essential for achieving normal neurodevelopmental and cognitive outcomes in individuals with PKU.