BackgroundObesity is a highly prevalent condition with important health implications. Face-to-face interventions to treat obesity demand a large number of human resources and time, generating a great burden to individuals and health system. In this context, the internet is an attractive tool for delivering weight loss programs due to anonymity, 24-hour-accessibility, scalability, and reachability associated with Web-based programs.ObjectiveWe aimed to investigate the effectiveness of Web-based digital health interventions, excluding hybrid interventions and non-Web-based technologies such as text messaging, short message service, in comparison to nontechnology active or inactive (wait list) interventions on weight loss and lifestyle habit changes in individuals with overweight and obesity.MethodsWe searched PubMed or Medline, SciELO, Lilacs, PsychNet, and Web of Science up to July 2018, as well as references of previous reviews for randomized trials that compared Web-based digital health interventions to offline interventions. Anthropometric changes such as weight, body mass index (BMI), waist, and body fat and lifestyle habit changes in adults with overweight and obesity were the outcomes of interest. Random effects meta-analysis and meta-regression were performed for mean differences (MDs) in weight. We rated the risk of bias for each study and the quality of evidence across studies using the Grades of Recommendation, Assessment, Development, and Evaluation approach.ResultsAmong the 4071 articles retrieved, 11 were included. Weight (MD −0.77 kg, 95% CI −2.16 to 0.62; 1497 participants; moderate certainty evidence) and BMI (MD −0.12 kg/m2; 95% CI −0.64 to 0.41; 1244 participants; moderate certainty evidence) changes were not different between Web-based and offline interventions. Compared to offline interventions, digital interventions led to a greater short-term (<6 months follow-up) weight loss (MD −2.13 kg, 95% CI −2.71 to −1.55; 393 participants; high certainty evidence), but not in the long-term (MD −0.17 kg, 95% CI −2.10 to 1.76; 1104 participants; moderate certainty evidence). Meta-analysis was not possible for lifestyle habit changes. High risk of attrition bias was identified in 5 studies. For weight and BMI outcomes, the certainty of evidence was moderate mainly due to high heterogeneity, which was mainly attributable to control group differences across studies (R2=79%).ConclusionsWeb-based digital interventions led to greater short-term but not long-term weight loss than offline interventions in overweight and obese adults. Heterogeneity was high across studies, and high attrition rates suggested that engagement is a major issue in Web-based interventions.