Background: Subclinical hypothyroidism (SH), defined as mild thyroid-stimulating hormone (TSH) elevation with normal free thyroxine (FT4) levels and no symptoms, is common during the first few years of life in Down syndrome (DS) and can be self-limiting. Our objective was to confirm that SH is usually a transitory disorder and to identify the factors associated with spontaneous remission. Methods: We reviewed clinical histories of patients from the Catalan Down Syndrome Foundation (CDSF) with DS and SH diagnosed before 5 y of age. SH was defined as TSH 5.5-25 μU/ml (6 mo-4 y) or 4.13-25 μU/ml (4-7 y), with FT4 0.89-1.87 ng/dl (6 mo-4 y) or 0.96-1.86 ng/dl (4-7 y). Results: Fifty-three patients with SH were identified, with an average age of 2.4 ± 1.1 y, median (range) TSH at diagnosis 7.1 (4.2-23.9 μU/ml), and median (range) FT4 1.1 (0.9-1.7 ng/dl). SH resolved spontaneously in 39 cases (73.6%), with TSH at the most recent visit (mean age 6.7 ± 1.4 y) 3.9 (1.8-12.7 μU/ml). The rate of remission was significantly higher in patients without goiter (94.9 vs. 28.6%) and in those who were negative for antithyroid antibodies (89.7 vs. 42.9%). Conclusion: SH in infants and preschool children with DS is usually a transitory disorder, with remission in >70% of cases. The absence of goiter and thyroid autoantibodies was associated with a greater rate of spontaneous remission in our study. © 2013 International Pediatric Research Foundation, Inc.