OBJECTIVE: To determine the effectiveness of interventions designed to improve outcomes in patients with multimorbidity in primary care and community settings. DESIGN: Systematic review. DATA SOURCES: Medline, Embase, CINAHL, CAB Health, Cochrane central register of controlled trials, the database of abstracts of reviews of effectiveness, and the Cochrane EPOC (effective practice and organisation of care) register (searches updated in April 2011). ELIGIBILITY CRITERIA: Randomised controlled trials, controlled clinical trials, controlled before and after studies, and interrupted time series analyses reporting on interventions to improve outcomes for people with multimorbidity in primary care and community settings. Multimorbidity was defined as two or more chronic conditions in the same individual. Outcomes included any validated measure of physical or mental health and psychosocial status, including quality of life outcomes, wellbeing, and measures of disability or functional status. Also included were measures of patient and provider behaviour, including drug adherence, utilisation of health services, acceptability of services, and costs. DATA SELECTION: Two reviewers independently assessed studies for eligibility, extracted data, and assessed study quality. As meta-analysis of results was not possible owing to heterogeneity in participants and interventions, a narrative synthesis of the results from the included studies was carried out. RESULTS: 10 studies examining a range of complex interventions totalling 3407 patients with multimorbidity were identified. All were randomised controlled trials with a low risk of bias. Two studies described interventions for patients with specific comorbidities. The remaining eight studies focused on multimorbidity, generally in older patients. Consideration of the impact of socioeconomic deprivation was minimal. All studies involved complex interventions with multiple components. In six of the 10 studies the predominant component was a change to the organisation of care delivery, usually through case management or enhanced multidisciplinary team work. In the remaining four studies, intervention components were predominantly patient oriented. Overall the results were mixed, with a trend towards improved prescribing and drug adherence. The results indicated that it is difficult to improve outcomes in this population but that interventions focusing on particular risk factors in comorbid conditions or functional difficulties in multimorbidity may be more effective. No economic analyses were included, although the improvements in prescribing and risk factor management in some studies could provide potentially important cost savings. CONCLUSIONS: Evidence on the care of patients with multimorbidity is limited, despite the prevalence of multimorbidity and its impact on patients and healthcare systems. Interventions to date have had mixed effects, although are likely to be more effective if targeted at risk factors or specific functional difficulties. A need exists to clearly identify patients with multimorbidity and to develop cost effective and specifically targeted interventions that can improve health outcomes.