Highlights ► Safety of intensified processes was analyzed by a checklist-based approach. ► A checklist was developed for process safety analysis on the basis of the protection layer concept. ► With real cases it was shown that several positive and negative effects on safety can be detected in process intensification. ► Negative and positive effects in the inherent safety layer are the most important and should be taken seriously. ► It is dangerous to assume that safety is always improved through intensification.