The present study, conducted in a first-episode psychotic sample, aims totest whether substance misuse, particularly cannabis use 1) is more frequent in patients than the general population, 2) is associated with a higher level of positive symptoms, a lower level of depressive symptoms and a worse premorbid adjustment at the onset, 3) is associated with an earlier age of onset and a better premorbid IQ. The study was conducted within the broader framework of the PICOS (Psychosis Incident Cohort Outcome Study), a multi-site collaborative research on incident cases of psychosis attending psychiatric services in the Veneto Region, Italy.