Acute poisoning is considered one of the most important medical emergencies, resulting in severe morbidity and mortality, and is an economic burden on governments. This study aimed to determine the extent of acute adult intoxication among the population located in the Najran area, Saudi Arabia, over the last 3 years (from January 2017 to December 2019). The study is a hospital-based retrospective observational study. The data of all acutely intoxicated adult patients were collected from patients’ files of King Khalid Hospital, the main hospital in the Najran area. In this study, the total number of intoxicated patients was 852. Patients were divided into three groups according to their age: 15–25 years, 26–35 years and >35 years. Accidental intoxication was predominant (64.6%), especially with therapeutic drugs (60.2%), predominantly acetaminophen and amphetamine, which intoxicated 24.5% and 23.4% of the patients, respectively. Moreover, this study showed that 10.6% of patients were intoxicated with overdoses of alcohol, mostly among patients aged over 35 years. Furthermore, the present study revealed that 23.9% of patients were intoxicated with household chemicals, especially Clorox bleach or Flash. Patients presented with a wide range of symptoms; some were even asymptomatic. Overall, patients’ outcomes were good; mortalities were few (1.2%), and most fatalities were found in patients aged over 35 years (60%). The present study showed that pharmaceutical drugs constituted the most common causative agents in acute intoxication. Household chemicals, especially Clorox bleach, Flash and pesticides, are highly implicated in the acute toxicity problem. Drug abuse, especially amphetamine and alcohol, still represents a great threat facing people from the Najran region. It is crucial to deliver effective public health education programmes to increase community awareness about the predisposing risk factors of acute toxicity, whether as overdoses or suicide attempts.