A higher incidence of primary congenital hypothyroidism (CH) has been related to increased sensitivity in neonatal screening tests. The benefit of treatment in mild cases remains a topic of debate. We evaluated the impact of reducing the blood-spot TSH cut-off (b-TSH) from 10 (Group 2) to 6 mIU/L (Group 1) in a public neonatal screening program. During the study period, 40% of 123 newborns with CH (n = 162,729; incidence = 1:1323) had b-TSH between 6 and 10 mIU/L. Group 1 patients had fewer clinical signs (p = 0.02), lower serum TSH (p < 0.01), and higher free T4 (p < 0.01) compared to those in Group 2 at diagnosis. Reducing the b-TSH cut-off from 10 to 6 mIU/L increased screening sensitivity, allowing a third of diagnoses, mainly mild cases, not being missed. However, when evaluating the performances of b-TSH cut-offs (6, 7, 8, 9, and 10 mIU/L), the lower values were associated with low positive predictive values (PPVs) and unacceptable increased recall rates (0.57%) for a public health care program. A proposed strategy is to adopt a higher b-TSH cut-off in the first sample and a lower one in the subsequent samples from the same child, which yields a greater number of diagnoses with an acceptable PPV.