In this multi-center cross-sectional study, we compared substance use patterns (SUPs) between patients with narcolepsy type 1 (NT1) and controls, and investigated, among patients, factors associated with the consumption of the main psychoactive substances. Methods: Adult patients with NT1 and controls completed questionnaires about tobacco, alcohol, and cannabis use patterns. Unadjusted bivariable then multivariate analyses (adjusted for sex, age, education, family status, and depression) were performed to compare SUPs between controls and patients, and to explore sociodemographic, psycho-behavioral, and clinical determinants of consumptions. Results: We included 235 patients (63.8 % women, 36.4 ± 14.7 years) and 166 controls (69.9 % women, 40.3 ± 14.4 years). Substances co-consumptions were frequent in both groups. Patients with NT1 were more frequently current smokers (32.3 % vs. 20.1 %, p < 0.01) or e-cigarettes users (12.1 % vs 2.4 %, p < 0.001) than controls, while no difference was observed for cannabis use and alcohol misuse. Only the increased likelihood of vaping remained significant in adjusted analysis. Among NT1 patients, smoking was associated with disrupted nighttime sleep (OR[95%CI] = 2.28[1.02-5.12], p < 0.05) and less obesity (OR = 0.24[0.09-0.59], p < 0.05). Alcohol misuse was associated with sleep paralysis (OR = 2.11[1.13-3.91], p < 0.05) and treatments (modafinil: OR = 2.14[1.15-4.01], p < 0.05; sodium oxybate: OR = 0.41[0.17-0.97], p < 0.05). Tobacco and cannabis consumptions were associated with lower physical activity (OR = 0.46 [0.24-0.87], p < 0.05 and OR = 0.25 [0.10-0.66], p < 0.01). Alcohol misuse and cannabis use were associated with rule breaking behaviors (OR = 5.89[1.61-21.60], p < 0.05 and OR = 8.52 [1.79-40.48], p = 0.01). Conclusion: Patients with NT1 do not seem less vulnerable to psychoactive substance use/misuse. Consumptions patterns are associated with multiple dimensions of the disease including sleep-related symptoms, comorbidities, treatments, and psycho-behavioral factors.