This STE report examines the safety, screening accuracy, therapeutic efficacy/effectiveness, cost-effectiveness, budget impact, and health system readiness of newborn screening for seven conditions (galactosemia, tyrosinemia type I, homocystinuria, sickle cell anemia, sickle cell/beta-thalassemia, sickle cell/hemoglobin C disease, and severe combined immunodeficiency), contextualized to the Alberta setting.