We aimed to interrogate sex differences in cardiac mechanics using two-(2D) and three-(3D) dimensional speckle tracking echocardiography (STE) in survivors of childhood cancers. 83 survivors (43 males) aged 25.6 ± 6.1 years at 16.0 ± 6.1 years after anthracycline therapy and 42 healthy controls (21 males) were studied. 2D STE was performed to assess LV linear deformation in three principal directions, while 3D STE was performed to assess LV ejection fraction, global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and global area strain (GAS). Receiver operating characteristic (ROC) curves were generated to to determine the usefulness of 2D and 3D echocardiographic indices to discriminate between survivors and controls. Survivors of both sex had significantly lower 2D and 3D strain indices compared with sex-specific controls (all p < 0.05). Among survivors, 2D GLS and GRS and all of the 3D indices were similar between males and females (all p > 0.05). Among cancer survivors, multivariate analysis revealed age at study (β = − 0.26, p = 0.022) as a significant determinant of 3D GLS. The area under the ROC curve for 3D GLS was the largest at 0.89 amongst all 3D and 2D strain parameters, while that of 2D GLS was 0.83. For 3D GLS, a cut-off of 16.4% had a sensitivity of 85.7% and a specificity of 80.7% of differentiating survivors from controls. Notwithstanding the finding of impaired LV myocardial mechanics, the present study did not reveal evidence of sexual dimorphism in cardiac mechanics in long term survivors of childhood cancers.