Herbal medicine is gaining popularity among healthcare providers and patients alike, for treating various health disorders. Main objective of this study was to determine the prevalence of herbal medicine use among the adult population in Najran, and to identify the factors associated with herbal medicine use. A cross-sectional descriptive study was conducted from September 2018 to January 2019 at Najran University Hospital in Najran, in which a total of 1000 randomly selected adult (> 18 years) patients were recruited. The data was collected using a structured questionnaire. The prevalence of herbal medicine use was found to be 46.1%. The majority of participants believed that using herbal products is safe (51.9%) and beneficial (62.7%). Some 44.5% of participants had previously used herbal products for treatment. Herbal medicine use was higher in patients with chronic diseases such as inflammatory bowel disease (63.0%), asthma (51.2%), diabetes (47.1%), cancer (46.7%), and hypertension (44.1%). The percentage of herbal medicine use among participants without chronic disease was found to be 43.5%. In conclusion, the prevalence of herbal medicine use is relatively low in Najran region when compared with other parts of Saudi Arabia. The most important determinants of herbal medicine use were increasing age, higher salary and chronic diseases.