Rapid tranquillization is a restrictive practice that remains widely used in mental health inpatient settings worldwide. Nurses are the professionals most likely to administer rapid tranquillization in mental health settings. To improve mental health practices, an enhanced understanding of their clinical decision-making when using rapid tranquillization is, therefore, important. The aim was to synthesize and analyse the research literature on nurses’ clinical decision-making in the use of rapid tranquillization in adult mental health inpatient settings. An integrative review was conducted using the methodological framework described by Whittemore and Knafl. A systematic search was conducted independently by two authors in APA PsycINFO, CINAHL Complete, Embase, PubMed and Scopus. Additional searches for grey literature were conducted in Google, OpenGrey and selected websites, and in the reference lists of included studies. Papers were critically appraised using the Mixed Methods Appraisal Tool, and the analysis was guided by manifest content analysis. Eleven studies were included in this review, of which nine were qualitative and two were quantitative. Based on the analysis, four categories were generated: (I) becoming aware of situational changes and considering alternatives, (II) negotiating voluntary medication, (III) administering rapid tranquillization and (IV) being on the other side. Evidence suggests that nurses’ clinical decision-making in the use of rapid tranquillization involved a complex timeline with various impact points and embedded factors that continuously influenced and/or were associated with nurses’ clinical decision-making. However, the topic has received scant scholarly attention, and further research may help to characterize the complexities involved and improve mental health practice.