Background: Efforts to improve the quality, safety, and efficiency of health care provision have often focused on changing approaches to the way services are organized and delivered. Continuous quality improvement (CQI), an approach used extensively in industrial and manufacturing sectors, has been used in the health sector. Despite the attention given to CQI, uncertainties remain as to its effectiveness given the complex and diverse nature of health systems. This review assesses the effectiveness of CQI across different health care settings, investigating the importance of different components of the approach. Methods: We searched 11 electronic databases: MEDLINE, CINAHL, EMBASE, AMED, Academic Search Complete, HMIC, Web of Science, PsycINFO, Cochrane Central Register of Controlled Trials, LISTA, and NHS EED to February 2019. Also, we searched reference lists of included studies and systematic reviews, as well as checking published protocols for linked papers. We selected randomized controlled trials (RCTs) within health care settings involving teams of health professionals, evaluating the effectiveness of CQI. Comparators included current usual practice or different strategies to manage organizational change. Outcomes were health care professional performance or patient outcomes. Studies were published in English. Results: Twenty-eight RCTs assessed the effectiveness of different approaches to CQI with a non-CQI comparator in various settings, with interventions differing in terms of the approaches used, their duration, meetings held, people involved, and training provided. All RCTs were considered at risk of bias, undermining their results. Findings suggested that the benefits of CQI compared to a non-CQI comparator on clinical process, patient, and other outcomes were limited, with less than half of RCTs showing any effect. Where benefits were evident, it was usually on clinical process measures, with the model used (i.e., Plan-Do-Study-Act, Model of Improvement), the meeting type (i.e., involving leaders discussing implementation) and their frequency (i.e., weekly) having an effect. None considered socioeconomic health inequalities.