Serum thyrotropin concentrations are frequently elevated during treatment of children with congenital hypothyroidism. It is unclear if elevated thyrotropin during early treatment indicates non‐optimal treatment. In a cohort of 49 children with congenital hypothyroidism, we studied the decline in serum thyrotropin concentration after initiating L‐thyroxine treatment, the relationship between elevated thyrotropin and treatment variables, and non‐compliance with the treatment as a possible cause of elevated thyrotropin. The initial mean dose of thyroxine was 8.5 (SD 3.3) μg/kg body weight/day: 71 % of the serum samples obtained 15‐21 days after the start of treatment had serum thyrotropin concentrations < 10 mU/1. Six children had no samples with serum thyrotropin < 10 mU/1 during the first 3 months of treatment. These children had a lower thyroxine dose prescribed, and serum thyrotropin was normalized when the dose was sufficiently increased. During treatment, from 6 weeks of age, serum thyrotropin > 10 mU/1 was related to a lower dose of thyroxine and lower serum thyroxine, and was not due to non‐compliance with treatment.