Objective To assess the effect of psychostimulant treatments on the 24-hour blood pressure (BP) profile of patients with narcolepsy type 1 (NT1). Methods Heart rate (HR) and BP were monitored for 24 hours and morning endothelial function was evaluated in 160 consecutive patients with NT1: 68 untreated (41 male, median age 34.9 years), 54 treated (32 male, median age 40.9 years), and 38 evaluated twice (21 male, median age 32 years), before and during treatment. Results Patients treated for NT1 showed higher 24-hour, daytime, and nighttime diastolic BP and HR values compared with the untreated group. Similarly, HR as well as 24-hour and daytime systolic BP were increased during treatment in the group evaluated twice. The combination of stimulant and anticataplectic drugs showed a synergistic effect on BP, without differences among stimulant categories. Based on 24-hour BP monitoring, hypertension was diagnosed in 58% of treated patients and in 40.6% of untreated patients. After adjustments for age, sex, and body mass index, the percentage of REM sleep remained associated with 24-hour hypertension in untreated and treated patients. Endothelial function was comparable in treated and untreated patients. Conclusions The finding that patients with NT1 treated with psychostimulants have higher diastolic BP and HR than untreated patients suggests an increased long-term risk of cardiovascular diseases that requires careful follow-up and specific management.