PURPOSE. The goal of this study was to establish sectorial and regional variability in the mechanical strain of peripapillary and mid-peripheral sclera in normal eyes from elderly human donors. METHODS. Ten pairs of normal eyes from human donors aged 57 to 90 years old were mechanically inflation-tested within 48 hours post mortem. The intact posterior scleral shells were pressurized from 5 to 45 mm Hg while the full-field threedimensional displacements of the scleral surface were measured using laser speckle interferometry. The displacement field was fit to continuous and differentiable analytical functions, from which the full strain tensor of the outer scleral surface was calculated. Mean maximum principal (tensile) strain was computed for eight circumferential sectors (45° wide) within the peripapillary and mid-peripheral regions surrounding the optic nerve head (ONH). RESULTS. Overall, the peripapillary sclera exhibited significantly higher tensile strain (1.2%) than mid-peripheral sclera (0.95%) for a 40 mm Hg IOP elevation (P < 0.00001). In the peripapillary region, the inferotemporal sector exhibited the highest tensile strain (1.45%) while the superior sector had the lowest (1.19%; P < 0.00001). Mid-peripheral scleral strains were lower but exhibited a similar sectorial pattern. CONCLUSIONS. Human posterior sclera exhibits complex regional mechanical behavior in response to acute IOP elevations from 5 to 45 mm Hg. Results indicate 1) the peripapillary sclera is subjected to significantly higher tensile strain than the adjacent mid-peripheral sclera, and 2) strains are significantly higher in the temporal and inferior quadrants of the peripapillary sclera, which may contribute to the increased prevalence of glaucomatous damage associated with these regions of the ONH. © 2012 The Association for Research in Vision and Ophthalmology, Inc.