OBJECTIVES: Patients in inpatient mental health settings face similar risks (eg, medication errors) to those in other areas of healthcare. In addition, some unsafe behaviours associated with serious mental health problems (eg, self-harm), and the measures taken to address these (eg, restraint), may result in further risks to patient safety. The objective of this review is to identify and synthesise the literature on patient safety within inpatient mental health settings using robust systematic methodology. DESIGN: Systematic review and meta-synthesis. Embase, Cumulative Index to Nursing and Allied Health Literature, Health Management Information Consortium, MEDLINE, PsycINFO and Web of Science were systematically searched from 1999 to 2019. Search terms were related to 'mental health', 'patient safety', 'inpatient setting' and 'research'. Study quality was assessed using the Hawker checklist. Data were extracted and grouped based on study focus and outcome. Safety incidents were meta-analysed where possible using a random-effects model. RESULTS: Of the 57 637 article titles and abstracts, 364 met inclusion criteria. Included publications came from 31 countries and included data from over 150 000 participants. Study quality varied and statistical heterogeneity was high. Ten research categories were identified: interpersonal violence, coercive interventions, safety culture, harm to self, safety of the physical environment, medication safety, unauthorised leave, clinical decision making, falls and infection prevention and control. CONCLUSIONS: Patient safety in inpatient mental health settings is under-researched in comparison to other non-mental health inpatient settings. Findings demonstrate that inpatient mental health settings pose unique challenges for patient safety, which require investment in research, policy development, and translation into clinical practice. PROSPERO REGISTRATION NUMBER: CRD42016034057.