Background: Subjective quality of life (S-QoL) is an important outcome measure in first-episode psychosis, but its associations with clinical predictors may vary across the illness course. In this study we examine the association pattern, including both direct and indirect effects, between specific predefined clinical predictors (insight, depression, positive psychotic symptoms and global functioning) and S-QoL the first ten years after a first-episode psychosis. Methods: Three hundred and one patients with a first-episode psychosis were included at first treatment, and reassessed at 3 months, 1 year, 2 years, 5 years and 10 years after inclusion. At 10-year follow-up 186 participated. S-QoL was assessed with Lehman's Quality of Life Interview. Applying a structural equation model, we investigated cross-sectional association patterns at all assessments between the predefined clinical predictors and S-QoL. Results: At baseline, only depression was significantly associated with S-QoL. At all follow-up assessments, depression and functioning showed significant associations with S-QoL. Insight was not associated with S-QoL at any of the assessments. Better insight, less depressive symptoms and less positive psychotic symptoms were all associated with higher functioning at all assessments. Functioning seems to mediate a smaller indirect inverse association between positive psychotic symptoms and S-QoL. The association pattern was stable across all follow-up assessments. Conclusions: Together with depression, functioning seems to be important for S-QoL. Functioning seems to be a mediating factor between positive symptoms and S-QoL. A focus on functional outcome continues to be important.