Introduction: The objective of this paper is to investigate the behavioural intention to use the Poison Information System (PIS) among healthcare professionals based on the extension of the Technology Acceptance Model. Methods: A quantitative approach used a five-point Likert scale questionnaire adapted from previous research. Data were obtained from 136 health professionals working in the Emergency Department of public hospitals in Malaysia. Results: A multiple linear regression model showed that approximately 40% of the variation in intention to use was related to positive attitude, staff category, and inversely to computer anxiety. Perceived usefulness, perceived ease of use, and computer usage were related to intention to use, but their correlation was accounted for by positive attitude, staff category, and computer anxiety. A factor analysis grouped positive attitude, intention to use, and perceived usefulness on Factor I and perceived ease of use, inverse computer anxiety, and computer habit on Factor II. Cluster analysis indicated three clusters. Gender, age, experience, and staff category were strongly inter-related; intention to use clustered with perceived ease of use and perceived usefulness; positive attitude clustered with computer habit; and the latter two clustered together. Conclusion: These findings show that positive attitude, staff category, and computer anxiety of healthcare professionals, working in emergency departments, may have the greatest effect on PIS usage.