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Background: Face-to-face brief interventions for problem drinking are effective, but they have found limited implementation in routine care and the community. Internet-based interventions could overcome this treatment gap. We investigated effectiveness and moderators of treatment outcomes in internet-based interventions for adult problem drinking (iAIs)., Methods and Findings: Systematic searches were performed in medical and psychological databases to 31 December 2016. A one-stage individual patient data meta-analysis (IPDMA) was conducted with a linear mixed model complete-case approach, using baseline and first follow-up data. The primary outcome measure was mean weekly alcohol consumption in standard units (SUs, 10 grams of ethanol). Secondary outcome was treatment response (TR), defined as less than 14/21 SUs for women/men weekly. Putative participant, intervention, and study moderators were included. Robustness was verified in three sensitivity analyses: a two-stage IPDMA, a one-stage IPDMA using multiple imputation, and a missing-not-at-random (MNAR) analysis. We obtained baseline data for 14,198 adult participants (19 randomised controlled trials [RCTs], mean age 40.7 [SD = 13.2], 47.6% women). Their baseline mean weekly alcohol consumption was 38.1 SUs (SD = 26.9). Most were regular problem drinkers (80.1%, SUs 44.7, SD = 26.4) and 19.9% (SUs 11.9, SD = 4.1) were binge-only drinkers. About one third were heavy drinkers, meaning that women/men consumed, respectively, more than 35/50 SUs of alcohol at baseline (34.2%, SUs 65.9, SD = 27.1). Post-intervention data were available for 8,095 participants. Compared with controls, iAI participants showed a greater mean weekly decrease at follow-up of 5.02 SUs (95% CI -7.57 to -2.48, p < 0.001) and a higher rate of TR (odds ratio [OR] 2.20, 95% CI 1.63-2.95, p < 0.001, number needed to treat [NNT] = 4.15, 95% CI 3.06-6.62). Persons above age 55 showed higher TR than their younger counterparts (OR = 1.66, 95% CI 1.21-2.27, p = 0.002). Drinking profiles were not significantly associated with treatment outcomes. Human-supported interventions were superior to fully automated ones on both outcome measures (comparative reduction: -6.78 SUs, 95% CI -12.11 to -1.45, p = 0.013; TR: OR = 2.23, 95% CI 1.22-4.08, p = 0.009). Participants treated in iAIs based on personalised normative feedback (PNF) alone were significantly less likely to sustain low-risk drinking at follow-up than those in iAIs based on integrated therapeutic principles (OR = 0.52, 95% CI 0.29-0.93, p = 0.029). The use of waitlist control in RCTs was associated with significantly better treatment outcomes than the use of other types of control (comparative reduction: -9.27 SUs, 95% CI -13.97 to -4.57, p < 0.001; TR: OR = 3.74, 95% CI 2.13-6.53, p < 0.001). The overall quality of the RCTs was high; a major limitation included high study dropout (43%). Sensitivity analyses confirmed the robustness of our primary analyses., Conclusion: To our knowledge, this is the first IPDMA on internet-based interventions that has shown them to be effective in curbing various patterns of adult problem drinking in both community and healthcare settings. Waitlist control may be conducive to inflation of treatment outcomes., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: DE has served as a consultant to/on the scientific advisory boards of Sanofi, Novartis, Minddistrict, Lantern, Schoen Kliniken, and German health insurance companies (BARMER, Techniker Krankenkasse). He is also a stakeholder of the Institute for health training online (GET.ON), which aims to implement scientific findings related to digital health interventions into routine care. RH's company owns the IP of the web applications that their data came from, as a basis for their contribution to the overall data set. HDV is the scientific director of Vision2Health, a company with the goal to implement evidence-based eHealth interventions. HR received a fee for participating in a brainstorm session on ehealth and bipolar disorders/PTSD organized by Sandoz. The remaining authors declare no competing interests.