Background: Although unapproved by the FDA for treating insomnia, trazodone is commonly prescribed in the US partly due to lack of scheduling, hence it’s perceived as safer than z-drugs and benzodiazepines. This study investigated trazodone abuse/dependence potential and safety risks. Methods: Cases involving trazodone or benzodiazepines (temazepam, triazolam, estazolam) frequently prescribed for insomnia were identified from the FDA Adverse Events Reporting System (FAERS), National Forensic Laboratory Information System (NFLIS) for confiscation data, and the American Association of Poison Control Centers’-National Poison Data System (AAPCC-NPDS). Drug-related falls risk was assessed from claims databases. Results: FAERS included 11,228 trazodone and 5120 benzodiazepine reports. Of these, drug-abuse and drug-dependence cases with trazodone were lower than benzodiazepines (drug-abuse: 6.4%/12.6%; drug-dependence: 1.1%/3.6%). Serious cases (81.8%/83.9%) and deaths (35.4%/36.0%), were similar between trazodone and benzodiazepines. NFLIS reported 612/1,575,874 (0.04%) drug-seizure cases that included trazodone. AAPCC-NPDS reported 22,225/1,446,011 (1.54%) total case mentions of trazodone/all pharmaceuticals and 8445 trazodone-related single-exposure cases. Falls risk (1year-period) in Medicare beneficiaries ≥65y and commercially-insured enrollees ≥18y was reported for trazodone and benzodiazepines: Medicare, 9.5%/11.3%; Commercially-insured: 4.6%/3.7%. Conclusions: Trazodone has abuse/dependence potential and important safety risks. Given limited data from well-controlled studies and off-label use, re-evaluation of trazodone prescribing rates in patients with insomnia is warranted.