Background Hazardous substances at the workplace can cause a wide variety of occupational incidents. This study aimed to investigate the nature and circumstances of acute occupational intoxications reported to the Dutch Poisons Information Center. Methods During a one-year prospective study, data on the circumstances and causes of the incident, the exposure(s) and clinical course, were collected by a telephone survey with victims of an acute occupational intoxication. Results We interviewed 310 patients. Most incidents occurred in industry (25%), building and installation industry (14%) and agriculture (10%). Patients were often exposed via multiple routes. Inhalation was the most common route of exposure (62%), followed by ocular (40%) and dermal contact (33%). Acids and alkalis were often involved. Exposure often occurred during cleaning activities (33%). The main root causes of these accidents were: technical factors such as damaged packaging (24%) and defective apparatus (10%), organizational factors such as lack of work instructions (44%) and poor communication or planning (31%), and personal factors such as disregarding work instructions (13%), not (adequately) using personal protective equipment (12%) and personal circumstances (50%) such as inaccuracy, time pressure or fatigue. The majority of the patients only reported mild health effects and recovered quickly (77% within 1 week). Conclusions Poison Center data on occupational exposures provide an additional source of knowledge and an important basis for poisoning prevention strategies related to hazardous substances at the workplace. These data are useful in deciding which risk mitigation measures are most needed in preventing future workplace injuries.