Abstract Context The apparent increased incidence of congenital hypothyroidism (CH) is partly due to increased detection of transient disease. Objective This work aims to identify predictors of transient CH (T-CH) and establish a predictive tool for its earlier differentiation from permanent CH (P-CH). Methods A retrospective cohort study was conducted of patients diagnosed with CH from 2006 to 2015 through Newborn Screening Ontario (NSO). Results Of 469 cases, 360 (76.8%) were diagnosed with P-CH vs 109 (23.2%) with T-CH. Doses of levothyroxine predicting T-CH were less than 3.9 μg/kg at age 6 months, less than 3.0 μg/kg at ages 1 and 2 years, and less than 2.5 μg/kg at age 3 years. Descriptive statistics and multivariable logistic modeling demonstrated several diverging key measures between patients with T-CH vs P-CH, with optimal stratification at age 1 year. Thyroid imaging was the strongest predictor (P < .001). Excluding imaging, significant predictors in the first year of life included thyroxine dose/kg (P < .001-.002), increase in thyrotropin (TSH) above the reference interval during treatment (P = .002), screening TSH (P = .03), and a history of maternal thyroid disease (P = .02). Based on the 1-year model without imaging, a risk score was developed to identify children with T-CH who may benefit from an earlier trial off therapy, to reduce excess medicalization and health care costs. Conclusion A levothyroxine dose of less than 3 μg/kg at ages 1 and 2 years and less than 2.5 μg/kg at age 3 years can be predictive of T-CH. A novel risk score was developed that can be clinically applied to predict the likelihood of a successful trial off therapy for a given patient at age 1 year.