Abstract Background: Psychotic depression (PD) is heavily understudied despite high mortality and the severe course of illness. A majority of the studies conducted so far are also largely based on selected clinical samples. The aim of this study was to examine the clinical characteristics of PD in a representative prospective birth cohort sample. Methods: The Northern Finland Birth Cohort 1966 is a well-known prospective population-based cohort including 12 058 people followed since mid-pregnancy. We identified 55 individuals with PD, analysed their characteristics and compared them with schizophrenia (SZ), non-psychotic depression (NPD), psychotic bipolar disorder (PBD) and other psychoses (PNOS). Results: The life-time prevalence of stable (no conversion to schizophrenia, bipolar disorder or schizoaffective disorder) PD was 0.5%. PD subjects were older than SZ and PNOS subjects during the first psychotic episode and compared to SZ, more often female. PD required hospitalization and transition to disability pension more often than NPD, but less often than SZ. Comorbid alcohol abuse disorder (44%) and personality disorder (40%) were highly common in PD. PNOS had a similar occupational outcome than PD but hospitalization rate was lower in the PNOS group. PBD and PD had mostly comparable outcomes. Conclusions: Our findings in a naturalistic cohort support the notion that the course of illness in PD is mostly similar to that of PBD, it is less severe than in schizophrenia, but worse than in non-psychotic depression. PD seems to have high psychiatric comorbidity.