Synchrotron x-ray microdiffraction has been applied to TSV characterization in various studies for nondestructive inspection with submicron resolution due to its high beam intensity and penetration depth. In this paper, the application of this technique to TSV investigations is examined and the correlation of the plastic deformation to the microstructure and extrusion behavior along with the effect of TSV dimensional scaling is examined. It is shown that the variability of the copper microstructure and resulting TSV behavior requires a larger number of samples in order to report statistically significant observations. The role of the microstructure in creating statistical scatter is demonstrated through microdiffraction measurements of grain orientation correlated with the observed peak widening, which shows that degraded TSV reliability is largely due to the high elastic anisotropy of copper. After taking the statistical variations into account, the scaling effect was clearly observed, with larger plastic deformation in 2μm diameter TSVs than in 5μm diameter TSVs consistent with microstructure variations. This is confirmed by TSV extrusion measurements, which show that the magnitude and statistical spread of the via extrusion for the 2μm diameter TSVs is higher than that of the 5μm diameter TSVs. These results, validated by thermomechanical simulation, demonstrate first that large sample sizes are required in copper TSV investigations due to high variability, which is not improved with scaling