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Study Objectives: This multi-center comparative cross-sectional study aimed to describe educational and occupational pathways, quantify effort/reward imbalance at work and identify factors associated with professional prognosis in patients with narcolepsy type 1 (NT1)., Methods: Adult patients with NT1 and controls answered online questionnaires (Epworth sleepiness Scale, Beck Depression Inventory II, Siegrist questionnaire, Adult Self-Report, and a questionnaire on academic and professional trajectories) and were compared using sex- and age-adjusted logistic regressions. Clinical, demographic and psycho-social factors associated with patients' professional prognosis, as assessed by a composite score based on occupational-related outcomes, were explored with a generalized linear model., Results: We included 235 patients (63.8% women, 36.4±14.7 years, 86.5% treated, 66.4% with childhood onset) and 166 controls (69.9% women, 40.3±14.4 years). No difference was observed between patients and controls for graduation, but patients reported more interruptions, absenteeism and lateness during schooling. No difference was observed for employment rate (69.5% vs 77.0%), but income was lower in patients who reported more unwanted changes in position and part-time work, with increased effort-reward imbalance (OR=2.28 95%CI[1.20-4.33], p=0.01). Impaired professional prognosis was associated with depression (p<0.0001) and attention disorders (p=0.03), while being narcoleptic during schooling was a protective factor (p=0.02)., Conclusions: Most patients with NT1 manage to achieve their careers goals, but at the cost of an effort/reward imbalance. Early diagnosis might allow a better adjustment to the disease. The strong impact of psycho-cognitive comorbidities on professional outcomes stresses the need to consider psycho-cognitivo-social dimensions in patient care., Clinical Trial Registration: Registry: ClinicalTrials.gov; Identifier: NCT03765892., (© 2025 American Academy of Sleep Medicine.)