Background Narcolepsy is a chronic disorder that requires lifelong management; however, few studies have evaluated disease burden of narcolepsy. We estimated the healthcare burden of narcolepsy in Japan using data from the Japan Medical Data Center health insurance claims database. Methods This was a retrospective analysis of clinical burden, healthcare resource utilization, and costs among incident narcolepsy cases and matched controls identified between January 1, 2014 and December 31, 2019. Results Of the 1317 incident cases; 889 (with 1778 controls) were analyzed for healthcare burden, 626 (with 1252 controls) for clinical journey, and 439 (no controls) for treatment patterns. The most common baseline comorbidity was non-narcolepsy sleep disorder (41.6 % cases vs 3.0 % controls), including insomnia (28.5 % vs 2.6 %) and sleep apnea (10.8 % vs 0.3 %; both p < 0.001). The most common nonsleep disorder comorbidities were depression (35.0 % vs 2.6 %), anxiety (30.4 % vs 2.7 %), and headache/migraine (18.1 % vs 5.5 %; all p < 0.001). Compared to controls, narcolepsy cases had more prescription claims in the year following index date (82.8 % vs 9.5 %; p < 0.001), higher rates of outpatient (2291.8 vs 674.9 visits/100 person-years; p < 0.001) and inpatient claims (56.8 vs 5.1/100 person-years; p < 0.001), and longer hospital stays (mean 2.9 vs 0.5 days; p < 0.001). Similarly, median HCRU costs were higher in cases than controls (total annual healthcare costs, $2531 vs $266; community pharmacy claims, $826 vs $47 per person; and outpatient claim costs, $1053 vs $188 per person year). Conclusions Narcolepsy carries a substantial comorbidity burden, a high rate of medication prescribing, and high healthcare resource use in Japan.