In order to understand the nature and causes through which Health Information Systems (HIS) can affect patient safety negatively, a systematic review with thematic synthesis of the qualitative studies was performed. 26 papers met our criteria and were included into content analysis. 40 error contributing factors in working with HIS were recognized. Upon which, 4 main categories of contributing factors were defined. Analysis of the semantic relation between contributing reasons and common types of errors in healthcare practice revealed 6 mechanisms that can function as secondary contributing reasons. Results of this study can support care providers, system designers, and system implementers to avoid unintended negative effects for patient safety.