Powder compacts manufactured by the pharmaceutical industry are usually produced by uniaxial compression of powders or granules. This process results in compacts that are anisotropic in their mechanical strength, but this hypothesis has received little attention in the past. In this work, compacts were produced from sorbitol granules using two distinctively different particle size fractions, two compaction speeds and a range of different tablet porosities. The compact tensile strength was assessed by diametral and biaxial compression and by flexural bending. Fracture mechanics, i.e. the critical stress intensity factors in mode I and II loading, and the construction of the fracture envelope were used to investigate failure mechanisms and strength anisotropy. The strength results were also analyzed statistically employing Weibull analysis and analysis of variance. Granule size and compaction speed were identified as major influence factors on tensile strength. The magnitude of the effects found, however, varied between the individual test configurations. Further processing of the Weibull moduli obtained from the different tests confirmed the anisotropy of powder compacts made by uniaxial compression. They also showed that the commonly used diametral compression test to obtain tensile strength values is the least sensitive measure to assess the influence of particle properties on mechanical strength. Biaxial testing was found to be able to detect small changes in crack and flaw structure as a result of small changes in the particle characteristics of sorbitol.