Subclinical hypothyroidism (SHT) is an asymptomatic condition defined by increased serum thyroid stimulating hormone (TSH) with normal free thyroid hormone levels. In this study, global left ventricular (LV) myocardial mechanics in patients with SHT by three-dimensional speckle tracking echocardiography (3D-STE) and the influence of levothyroxine therapy on 3D-STE related parameters was evaluate. We used 32 consecutive patients with untreated SHT (10 males and 22 females, mean age: 50.7 ± 12.7 years) and 30 age-and gender-matched healthy volunteers (10 males and 20 females, mean age: 48.7 ± 14.2 years). Evothyroxine replacement therapy was prescribed to all SHT patients, and the euthyroid state is achieved by levothyroxine therapy the following year. The untreated SHT patients had significantly lower global longitudinal strain (GLS), global circumferential strain (GCS) and global area strain (GAS) values as compared to our controls, and the differences between two groups were statistically significant (P < 0 05). Global mechanical index (GMI) in SHT patients after therapy was significantly higher than that in the SHT patients before therapy [−492.7 ± 6.4 (%× ) vs. −386.3 ± 48.6 (%× , unit of GMI), P < 0 001], whereas GMI was still lower in SHT patients after therapy than the controls [−492.7 ± 6.4 (%× ) vs. −630.8 ± 64.8 (%× ), P < 0 001]. The receiver-operating characteristic (ROC) analysis showed that GMI is the best echocardiographic predictor of patients who developed myocardial dysfunction during the follow-up [AUC = 0.947, 95% CI = 0.900-0.994, with a sensitivity of 84.8% and a specificity of 92.4%, and optimal cut-off value for GMI was 473.2 (%× )]. We showed that 3D-STE and the GMI can be used for early detection of LV myocardial impairment and reversal of impairment in patients with SHT after therapy.