The equation of state and high-pressure behaviour of a natural sample of prehnite from Kuruman, South Africa, Ca2.07(Al0.98,Mn0.02)(AlSi3.09O10)(OH)2, have been investigated using single crystal X-ray diffraction up to 9.75(3) GPa. A second-order Birch–Murnaghan equation-of-state fit to the isothermal P-V data below 8.7 GPa yields values of K0T = 109.29(18) GPa and K0′ = 4. A third-order Birch-Murnaghan equation fit to the P-V data results in K′ values equal to four, within an estimated standard deviation. The compressibility of a, b, and c unit-cell parameters is non-linear and strongly anisotropic, with room-pressure moduli of Ka0 = 83.5(7) GPa, Kb0 = 113(1) GPa, and Kc0 = 146(3) GPa and K′a0 =4.5(3), K′b0 = 1.3(3), and K′c0 = 8.8(8). Intensity data were collected over the entire pressure range. Bond lengths and angles, refined in the average space group Pncm, suggest that the structure compresses uniformly. Above 8.7 GPa there is an additional softening of the volume and the b-axis, but the average structure is maintained across the transition.