Left ventricular (LV) hypertrophy and one of its inducers, the fibroblast growth factor-23 (FGF-23) were found to be associated with unfavourable outcome in end-stage renal disease (ESRD) patients. We sought to investigate the influence of hemodialysis (HD), increased LV mass and FGF-23 on LV mechanics using three-dimensional (3D) speckle tracking echocardiography. Forty-four ESRD patients on maintenance HD were examined just before and immediately after HD, and were compared to 44 normal controls (NC). Transthoracic 3D recordings were obtained using multi-beat reconstruction from 6 consecutive cardiac cycles. LV mass index (LVMi) was evaluated and 3D speckle tracking analysis was performed to calculate global longitudinal (GLS), circumferential (GCS), area (GAS) and radial (GRS) peak systolic strain. Serum FGF-23 levels were also measured. Strain values improved in all directions after HD [pre- vs. post-HD; GLS: -20(3) vs. -21(6), GCS: -20(4) vs. -22(7), GAS: -33(5) vs. -35(10), GRS: 50(12) vs. 53.5(20) %, all p < 0.01]. LVMi was remarkably increased in our patients [ESRD vs. NC; 136(46) vs. 71(8) g/m(2), p < 0.001]. Elevated FGF-23 levels were associated with increased LV mass (ρ = 0.581, p < 0.001). LVMi was inversely related to pre-HD GCS (ρ = 0.626, p < 0.001) and post-HD GCS (ρ = 0.761, p < 0.001), GAS (ρ = 0.534, p < 0.05) and GRS (ρ = -0.639, p < 0.01). Serum FGF-23 levels correlated with post-HD GAS (ρ = 0.513, p < 0.01) and GRS (ρ = -0.512, p < 0.05). HD treatment results in immediate improvement in all strain directions. Besides inducing LV hypertrophy, FGF-23 may play a role in the deterioration of LV mechanics in patients with ESRD.