Context: Subclinical hypothyroidism is a common condition that may lead to impaired cardiac function. Objective: This study sought to examine the effects of levothyroxine treatment in patients with subclinical hypothyroidism and heart disease. Design: This was a register-based historical cohort study. Setting and Participants: The study was composed of Danish primary care patients and hospital outpatients age 18 years and older with established heart disease who were diagnosed with subclinical hypothyroidism in 1997-2011. Patients were stratified according to whether they claimed a subsequent prescription of levothyroxine. Event ratesandincidence rate ratios (IRR)were calculated by use of time-dependent multivariable Poisson regression models. Main Outcome Measures: Measures included all-cause mortality and major adverse cardiac events (MACEs), defined as cardiovascular death, fatal or nonfatal myocardial infaction and stroke, and all-cause hospital admissions. Results: Of 61 611 patients with a diagnosis of cardiac disease having their first time thyroid function testing, 1192 patients with subclinical hypothyroidism(meanage 73.6 [SD±13.3] y,63.8%female) were included, of whom 136 (11.4%) were treated with levothyroxine. During a median follow-up time of 5.6 y (interquartile range, 6.5 y), 694 (58.2%) patients died. Patients treated with levothyroxine displayed no significantly increased risk of all-cause mortality (adjusted IRR, 1.17; 95%confidence interval [CI], 0.90-1.52), MACE (adjusted IRR, 1.08; 95%CI, 0.80-1.45), or hospital admission (adjusted IRR, 0.94; 95%CI, 0.71-1.24), when compared with patients not treated with levothyroxine. Conclusion: Levothyroxine treatment in patients with subclinical hypothyroidismandheart disease was not associated with a significant benefit nor risk of all-cause mortality, MACE, or hospital admission in this large real-world cohort study. (J Clin Endocrinol Metab 101: 4170-4177, 2016). Copyright © 2016 by the Endocrine Society.