Background: Many healthcare professionals use smartphones and tablets to inform patient care. Contemporary research suggests that handheld computers may support aspects of clinical diagnosis and management. This systematic review was designed to synthesise high quality evidence to answer the question; Does healthcare professionals' use of handheld computers improve their access to information and support clinical decision making at the point of care?. Methods. A detailed search was conducted using Cochrane, MEDLINE, EMBASE, PsycINFO, Science and Social Science Citation Indices since 2001. Interventions promoting healthcare professionals seeking information or making clinical decisions using handheld computers were included. Classroom learning and the use of laptop computers were excluded. Two authors independently selected studies, assessed quality using the Cochrane Risk of Bias tool and extracted data. High levels of data heterogeneity negated statistical synthesis. Instead, evidence for effectiveness was summarised narratively, according to each study's aim for assessing the impact of handheld computer use. Results: We included seven randomised trials investigating medical or nursing staffs' use of Personal Digital Assistants. Effectiveness was demonstrated across three distinct functions that emerged from the data: accessing information for clinical knowledge, adherence to guidelines and diagnostic decision making. When healthcare professionals used handheld computers to access clinical information, their knowledge improved significantly more than peers who used paper resources. When clinical guideline recommendations were presented on handheld computers, clinicians made significantly safer prescribing decisions and adhered more closely to recommendations than peers using paper resources. Finally, healthcare professionals made significantly more appropriate diagnostic decisions using clinical decision making tools on handheld computers compared to colleagues who did not have access to these tools. For these clinical decisions, the numbers need to test/screen were all less than 11. Conclusion: Healthcare professionals' use of handheld computers may improve their information seeking, adherence to guidelines and clinical decision making. Handheld computers can provide real time access to and analysis of clinical information. The integration of clinical decision support systems within handheld computers offers clinicians the highest level of synthesised evidence at the point of care. Future research is needed to replicate these early results and to identify beneficial clinical outcomes.