© 2015 Society of Biological Psychiatry. Background Hippocampal dysfunction and volume reductions have been reported in patients with schizophrenia and bipolar disorder. The hippocampus consists of anatomically distinct subfields. We investigated to determine whether in vivo volumes of hippocampal subfields differ between clinical groups and healthy control subjects. Methods Clinical examination and magnetic resonance imaging were performed in 702 subjects (patients with schizophrenia spectrum [n = 210; mean age, 32.0 ± 9.3 (SD) years; 59% male], patients with bipolar spectrum [n = 192; mean age, 35.5 ± 11.5 years; 40% male] and healthy control subjects [n = 300; mean age, 35.3 ± 9.9 years; 53% male]). Hippocampal subfield volumes were estimated with FreeSurfer. General linear models were used to explore diagnostic differences in hippocampal subfield volumes, covarying for age, intracranial volume, and medication. Post hoc analyses of associations to psychosis symptoms (Positive and Negative Syndrome Scale) and cognitive function (verbal memory [California Verbal Learning Test, second edition] and IQ [Wechsler Abbreviated Scale of Intelligence]) were performed. Results Patient groups had smaller cornu ammonis (CA) subfields CA2/3 (left, p = 7.2 × 10-6; right, p = 2.3 × 10-6), CA4/dentate gyrus (left, p = 1.4 × 10-5; right, p = 2.3 × 10-6), subiculum (left, p = 3.7 × 10-6; right, p = 2.8 × 10-8), and right CA1 (p =.006) volumes than healthy control subjects, but smaller presubiculum volumes were found only in patients with schizophrenia (left, p = 6.7 × 10-5; right, p = 1.6 × 10-7). Patients with schizophrenia had smaller subiculum (left, p =.035; right, p =.031) and right presubiculum (p =.002) volumes than patients with bipolar disorder. Smaller subiculum volumes were related to poorer verbal memory in patients with bipolar disorder and healthy control subjects and to negative symptoms in patients with schizophrenia. Conclusions Hippocampal subfield volume reductions are found in patients with schizophrenia and bipolar disorder. The magnitude of reduction is greater in patients with schizophrenia, particularly in the hippocampal outflow regions presubiculum and subiculum.