Context: Duration of untreated psychosis (DUP) is the time from manifestation of the first psychotic symptom to initiation of adequate treatment. It has been postulated that a longer DUP leads to a poorer prognosis. If so, outcome might be improved through earlier detection and treatment. Objectives: To establish whether DUP is associated with prognosis and to determine whether any association is explained by confounding with premorbid adjustment. Data Sources: The CINAHL (Cumulative Index to Nursing and Allied Health), EMBASE, MEDLINE, and PsychLIT databases were searched from their inception dates to May 2004. Study Selection: Eligible studies reported the relationship between DUP and outcome in prospective cohorts recruited during their first episode of psychosis. Twenty-six eligible studies involving 4490 participants were identified from 11 458 abstracts, each screened by 2 reviewers. Data Extraction: Data were extracted independently and were checked by double entry. Sensitivity analyses were conducted excluding studies that had follow-up rates of less than 80%, included affective psychoses, or did not use a standardized assessment of DUP. Data Synthesis: Independent meta-analyses were conducted of correlational data and of data derived from comparisons of long and short DUP groups. Most data were correlational, and these showed a significant association between DUP and several outcomes at 6 and 12 months (including total symptoms, depression/anxiety, negative symptoms, overall functioning, positive symptoms, and social functioning). Long vs short DUP data showed an association between longer DUP and worse outcome at 6 months in terms of total symptoms, overall functioning, positive symptoms, and quality of life. Patients with a long DUP were significantly less likely to achieve remission. The observed association between DUP and outcome was not explained by premorbid adjustment. Conclusions: There is convincing evidence of a modest association between DUP and outcome, which supports the case for clinical trials that examine the effect of reducing DUP. ©2005 American Medical Association. All rights reserved.