Aim: Defining diagnosis is complex in early psychosis, which may delay the introduction of an appropriate treatment. The dichotomy of affective and non-affective psychosis is used in clinical setting but lacks scientific basis. In this study, we explore the clinical relevance of this dichotomy on the basis of clinical variables in a sample of first episode psychosis patients. Method: We conducted a prospective study in a sample of 330 first episode psychosis treated at an early intervention program. Affective and non-affective psychosis patients were compared on premorbid history, baseline data, outcomes and course of symptoms over the three years of treatment. Results: Affective psychosis patients (22.42%) were more likely to be female, and had a shorter duration of untreated psychosis. The longitudinal analyses revealed that positive symptoms remained higher over the entire follow-up in the non-affective subgroup. A higher degree of variability of manic symptoms and a significantly better insight after 6 months were observed in the affective subgroup. No difference were observed regarding depressive and negative symptoms. At discharge, only the environmental quality of life and insight recovery were better in affective psychosis. Conclusions: Our study suggests that despite marginal differences at baseline presentation, these subgroups differ regarding outcome, which may require differentiation of treatment and supports the utility of this dichotomy.