Aim: To analyze the factors that might allow an early discrimination between permanent (P) and transient (T) congenital hypothyroidism (CH). Methods: Clinical, biochemical and imaging data of 64 children with eutopic gland, who were positively screened and treated for CH during the period 1998-2011, were retrospectively analyzed. Results: During a 3-year treatment period, the mean doses of L-thyroxine (L-T4) per kilogram of body weight at various times were significantly lower in the 46 children with T CH than in the remaining 18 with P CH. No patients with T CH had required any increment of the doses of L-T4 per kilogram of body weight to maintain normal thyroid-stimulating hormone levels over time, whereas 16/18 children with P CH during the same period had needed some dose increments (p < 0.0001). Conclusions: (a) L-T4 requirements >4.9 µg/kg/day at 12 months or >4.27 µg/kg/day at 24 months are highly suggestive of P CH, irrespective of gland ultrasonography; (b) L-T4 requirements <1.7 µg/kg/day at 12 months or <1.45 µg/kg/day at 24 months are highly suggestive of T CH, at least in the cases with eutopic gland, and (c) the analysis of L-T4 requirements during the first years of treatment might allow an early discrimination between T and P CH in the cases with eutopic gland.