Benzodiazepine receptor agonists (BZs) are medications to be used with caution, not only for long-time users, but also for first-time users. This study aimed to compare the use of BZs or central nervous system (CNS) agents in first-time BZs users (FU) and continuing BZs users (CU). Using a large health insurance claims database in Japan, BZs users aged ≥40 years in 2013 who were opioid non-users without hospitalization were classified into FU or CU, by use of BZs in the first half-year. BZs or CNS agent use at the index date (the first date BZs were dispensed in the latter year) was investigated as follows: (1) proportion of patients with prescriptions of BZs for use as needed (BZs-AN), (2) daily number of BZs or CNS agents, and (3) daily standardized dose of BZs or CNS agents. More individuals in the FU group (3,162/16,576; 19%) than in the CU group (7,627/46,088; 17%) received BZs-AN (p＜0.001); 87% of the FU group vs 62% of the CU group used single BZs (p＜0.001), and 53% vs 24% used less than 5 mg/day of equivalent diazepam (p＜0.001). A similar trend was found for CNS agents. Numbers or doses of BZs or CNS agents decreased with increasing age in both groups. However, some first-time users aged 70-74years started with ≥2 types of BZs or ≥10 mg/day of equivalent diazepam. Overall, BZs for outpatients without opioids were started carefully, but a prescription review was necessary for some patients, requiring more effort from healthcare providers.