Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: College students are increasingly reporting common mental health problems, such as depression and anxiety, and frequently encounter barriers to seeking traditional mental health treatments. Digital mental health interventions, such as those delivered via the web and apps, offer the potential to improve access to mental health treatment. Objective: This study reviews the literature on digital mental health interventions focused on depression, anxiety, and enhancement of psychological well-being among samples of college students to identify the effectiveness, uptake, and adoption of such programs. Methods: We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the search strategy was conducted by a medical research librarian in the following databases: MEDLINE (Ovid), EMBASE (Elsevier), PsycINFO (EbscoHost), the Cochrane Library (Wiley), and Web of Science (Thomson Reuters) databases (from the date of inception to December 2017). Data were synthesized using a systematic narrative synthesis framework and formal quality assessments were conducted to address risk of bias. Results: A total of 65 studies met inclusion criteria. The majority of interventions (n = 51) were delivered via website, and the most common intervention was internet-based cognitive behavioral therapy (iCBT; n = 15). Many programs (n = 27) featured human support in the form of coaching. The majority of studies (n = 35) did not present any usability or acceptability outcomes, and few studies examined broad implementation of digital mental health interventions on college campuses (n = 3). Conclusions: Results suggest that digital mental health interventions can be effective for improving depression, anxiety, and psychological well-being among college students, but more rigorous studies are needed to ascertain the effective elements of these interventions. Continued research on improving the user experience of, and thus user engagement with, these programs appears vital for the sustainable implementation of digital mental health on college campuses.