A large percentage of molecular compounds can crystallize in different hydration states. Although hydrated and anhydrous crystal forms can exhibit different physical properties (e.g., solubility, stability, mechanical strength), establishing the contribution water makes to the properties can be elusive. Anhydrous (UA) and dihydrate (UAD) crystal forms of uric acid share a remarkably similar two-dimensional layer structure, though the presence or absence of water between the layers imparts these crystal forms with dramatically different mechanical properties. The quantitative and qualitative differences in how these two materials respond to uniaxial stress were investigated with nanoindentation and atomic force microscopy (AFM) imaging normal to the layer direction. Overall, UA was found to be both substantially harder and more brittle than UAD. Load-displacement curves and AFM images of the UA crystal surface postindent reveal slip planes in preferred crystallographic directions and oriented crack formation at higher load forces. UAD was markedly softer and also exhibited substantial creep in response to indentation. Time lapsed images of UAD indents suggest that some amount of "self-healing" on the surface may be possible at shallow indentation depths of ∼100 nm.