Background: The relationship of panic attacks (PA), panic disorder (PD) and agoraphobia (AG) is controversial. The aim of the current study is to prospectively examine the 10-year natural course of PA, PD and AG in the first three decades of life, their stability and their reciprocal transitions. Methods: DSM-IV syndromes were assessed via Composite International Diagnostic Interview – Munich version in a 10-year prospective-longitudinal community study of 3,021 subjects aged 14–24 years at baseline. Results: (1) Incidence patterns for PA (9.4%), PD (with and without AG: 3.4%) and AG (5.3%) revealed differences in age of onset, incidence risk and gender differentiation. (2) Temporally primary PA and PD revealed only a moderately increased risk for subsequent onset of AG, and primary AG had an even lower risk for subsequent PA and PD. (3) In strictly prospective analyses, all baseline groups (PA, PD, AG) had low remission rates (0–23%). Baseline PD with AG or AG with PA were more likely to have follow-up AG, PA and other anxiety disorders and more frequent complications (impairment, disability, help-seeking, comorbidity) as compared to PD without AG and AG without PA. Conclusions: Differences in incidence patterns, syndrome progression and outcome, and syndrome stability over time indicate that AG exists as a clinically significant phobic condition independent of PD. The majority of agoraphobic subjects in this community sample never experienced PA, calling into question the current pathogenic assumptions underlying the classification of AG as merely a consequence of panic. The findings point to the necessity of rethinking diagnostic concepts and DSM diagnostic hierarchies.