Objectives: Data show that family members of ICU patients may have high levels of anxiety, depression, posttraumatic stress disorders, and/or complicated grief. This was previously referred to as post-intensive care syndrome-family. We systematically review randomized controlled trials for post-intensive care syndrome-family. Data Sources: Systematic research in databases (Pubmed, EMBASE, PsycINFO, CINHAL for articles published between January 2000 and October 2019). Study Selection: Interventions in randomized controlled trials for post-intensive care syndrome-family in relatives of adult ICU patients. Data Extraction: Review, quality assessment, and risk assessment for bias of eligible publications were performed along recommended guidelines for each investigation. Quality assessment graded studies into “strong” ( n = 5), “moderate” ( n = 4), and “weak” ( n = 2). Data Synthesis: Out of 2,399 publications, 11 investigations were found eligible (3,183 relatives of ICU patients). Studies addressed interventions during ICU stay ( n = 6), during the post-ICU period ( n = 4), or both ( n = 1). Two studies included relatives of dying/deceased patients. One study implemented end-of-life conferences and showed reduced prevalence of posttraumatic stress disorder (45% vs 69%; p = 0.01), anxiety (45% vs 67%; p = 0.02), and depression (29% vs 56%; p = 0.003). Family conferences with a physician and proactive participation of a nurse reduced anxiety-scores ( p = 0.01) without reducing anxiety prevalence (33.3% vs 52.3%; p = 0.08). Other studies failed to improve symptoms or reduce prevalence of post-intensive care syndrome-family. Interestingly, condolence letters may even increase prevalence of posttraumatic stress disorder (52.4% vs 37.1%; p = 0.03). Meetings without the presence of ICU physicians were shown to increase Impact of Event Scale-Revised scores (25.9 vs 21.3; p = 0.0495). Conclusions: Only few data are available on interventions for post-intensive care syndrome-family. It appears that proactive communication and provision of information seems pivotal for post-intensive care syndrome-family treatment. Interestingly, some interventions may even worsen post-intensive care syndrome-family. In the light of the relevance of post-intensive care syndrome-family in daily ICU care, more high-quality data seems urgently needed.