Severe obesity is an increasingly prevalent condition and is often associated with long-term comorbidities, reduced survival and higher healthcare costs. Non-surgical methods avoid the side effects, complications and costs of surgery, but it is unclear which non-surgical method is most effective. The objective of this article was to systematically review the effectiveness of lifestyle interventions compared to standard or minimal care for weight loss in adults with severe obesity. MEDLINE, EMBASE, CENTRAL, databases of on-going studies, reference lists of any relevant systematic reviews and the Cochrane Library database were searched from inception to February 2016 for relevant randomized controlled trials (RCTs). Inclusion criteria were participants with severe obesity (body mass index [BMI] > 40 kg/m2 or BMI > 35 kg/m2 with comorbidity) and interventions with a minimal duration of 12 weeks that were multi-component combinations of diet, exercise and behavioural therapy. Risk of bias was evaluated using the Cochrane risk of bias criteria. Meta-analysis was not possible because of methodological heterogeneity. Seventeen RCTs met the inclusion criteria. Weight change in kilograms of participants from baseline to follow-up was reported for 14 studies. Participants receiving the lifestyle intervention had a greater decrease in weight than participants in the control group for all studies (1.0-11.5 kg). Lifestyle interventions varied greatly between the studies. Overall lifestyle interventions with combined diet and exercise components achieved the greatest weight loss. Lifestyle interventions for weight loss in adults with severe obesity were found to result in increased weight loss when compared to minimal or standard care, especially those with combined diet and exercise components.