BackgroundLow engagement with self-guided online programs limits the potential of these programs to provide effective and low-cost treatment of mild to moderate depression and anxiety at scale. Identifying factors that increase uptake and adherence in self-guided online programs may facilitate the development of targeted implementation strategies to increase engagement with these programs in the community. Using data from a randomized controlled trial of a self-guided online program for depression and anxiety, the aim of this study was to identify predictors of the acceptability of internet-based psychological programs, and engagement (uptake and adherence) with the online program tested in the trial. MethodsA total of 556 community members with elevated symptoms of depression or anxiety were recruited via social media into the two active conditions of a three-arm randomized controlled trial. This trial tested the effectiveness of a 7-week self-guided online program for depression and anxiety called myCompass 2, delivered with or without an Engagement-Facilitation Intervention. Predictors of uptake (accessing at least one therapeutic module of the program), adherence (modules completed), and acceptability of internet-based psychological programs (Unified Theory of Acceptance and Use of Technology, UTAUT scale) were examined, including demographics, mental health status, help-seeking attitudes, stigma, acceptability of internet programs, and personality factors. ResultsLogistic regression demonstrated that higher levels of conscientiousness (OR = 1.06, p = .026, 95% CI =1.01–1.12), and acceptability of internet-based psychological programs (OR = 1.09, p = .005, 95% CI =1.03–1.16) predicted greater uptake, and that failing to complete a module was predicted by lower levels of acceptability (OR = 0.88, p = .027, 95% CI =0.78–0.99). Linear regression showed that higher levels of agreeableness (t = 4.66, p < .001), lower levels of stigma (t = −2.28, p = .023) and more positive help-seeking attitudes (t = 2.05, p = .041) predicted higher acceptability attitudes. DiscussionAcceptability of internet-based psychological programs was identified as a factor that increased both uptake and adherence to the myCompass 2 program. Efforts to increase the acceptability of these programs may improve engagement with these programs in the community. It may also be useful to consider personality traits and clinical profiles when considering the appropriate audience for self-guided internet interventions.