Background: The study of individuals at clinical high risk (CHR) for psychosis provides an important opportunity for unraveling pathological mechanisms underlying schizophrenia and related disorders. A small number of diffusion tensor magnetic resonance imaging (DTI) studies in CHR samples have yielded anatomically inconsistent results. The present study is the first to apply tract-based spatial statistics (TBSS) to perform a whole-brain DTI analysis in CHR subjects. Methods: A total of 28 individuals meeting CHR criteria and 34 healthy controls underwent DTI. TBSS was used for a group comparison of fractional anisotropy (FA), as well as axial, radial, and mean diffusivity (AD, RD, and MD). Conversion to psychosis was monitored during a mean follow-up period of 12.3 months. Results: The rate of conversion to psychosis was relatively low (4%). TBSS revealed increased MD in several clusters in the right hemisphere, most notably in the superior longitudinal fasciculus (SLF), posterior corona radiata, and corpus callosum (splenium and body). Increased RD was restricted to a smaller area in the posterior parietal lobe. Conclusion: We present further evidence that white matter microstructure is abnormal in CHR individuals, even in a sample in which the vast majority do not transition to psychosis over the following year. In accord with previous studies on CHR individuals and patients with early-onset schizophrenia, our findings suggest an important pathological role for the parietal lobe and especially the SLF. The latter is known to undergo particularly dynamic microstructural changes during adolescence and early adulthood, a critical phase for the development of psychotic illness.