The decision to mandate, finance, and implement a universal newborn hearing screening (UNHS) requires the evaluation of its therapy-directed benefit by comparing (1) a procedure employing a UNHS with (2) a targeted screening for at-risk babies for neonatal hearing disorders and (3) a procedure without systematic screening. In a cohort study the outcome of the UNHS program of Hessen in 2005 with 17,439 screened newborns was analyzed. Validity, effectiveness, and efficiency were evaluated and compared to a sample of 98 Hessian and 355 German children who were detected in 2005 as hearing-impaired but not by an UNHS. The UNHS group had a PASS rate of 97.0%. Forty-nine hearing-impaired children were diagnosed at a median age of 3.1 months and treated at a median age of 3.5 months. Corresponding values for the Hessian non-UNHS group were 17.8 and 21.0 months. For Germany the median age at diagnosis was 39.0 months. The age at therapy onset correlated negatively with parameters of speech/language and psychosocial development. A targeted screening would have resulted in a low sensitivity of 65.3%. Hence, a UNHS is the most effective way to an early therapy of neonatal hearing disorders with an optimal outcome.