Off-label prescribing is very common among physicians, particularly among psychiatrists and there is limited information regarding the extent of the unapproved drug use in Makkah city. The objective of this study was to assess the prevalence of off-label indications for antidepressant, antipsychotic and antiepileptic and the strength of evidence supporting use of the prescribed drug for the respective indication. A case sectional study was conducted on 15,955 prescriptions from 1 October 2018 to 6 January 2019 based on patient medication records obtained from an electronic medical record (EMRs) - health information system (HIS) from King Abdulaziz Hospital in Makkah city, Saudi Arabia. Two official databases (Micromedex and Lexicomp) were used to evaluate dual primary outcomes the determination off-label and on-label prescriptions and the level of evidence supporting the off-label indications. It showed that in 3 months there were 15,955 prescriptions concerning antipsychotics, antidepressants and antiepileptics drugs were issued to 5292 patients. Out of total 15,955 prescriptions, about 2218 (13.9%) prescriptions were off-label prescriptions for 29 drugs. The most frequently prescribed by class, were antidepressants 1025 (46.3%) followed by antipsychotics 1005 (45.3%) then antiepileptics 188 (8.5%). Off-label drugs use is common in psychiatric department and when physicians prescribed antidepressants, antipsychotics and antiepileptics for off-label indication, most of these prescribed indications were not supported by strong scientific evidences. The risks and benefits of off-label use should be carefully weighed up prior to prescribing these agents. Key words: Off-label, antipsychotics, antiepileptics, psychiatric, case sectional study.