ABSTRACT: BACKGROUND:The rapid increase in mental health disorders has prompted a call for greater focus on mental health promotion and primary prevention. Web- and mobile app-based interventions present a scalable opportunity. Little is known about the influence of human support on the outcomes of these interventions. OBJECTIVE:This study aimed to compare the influence of 3 modes of human support on the outcomes (ie, mental health, vitality, depression, anxiety, stress, life satisfaction, and flourishing) of a 10-week, Web- and mobile app-based, lifestyle-focused mental health promotion intervention among a healthy adult cohort. METHODS:Participants were recruited voluntarily using a combination of online and offline advertising. They were randomized, unblinded into 3 groups differentiated by human support mode: Group 1 (n=201): standard-fully automated emails (S); Group 2 (n=202): standard plus personalized SMS (S+pSMS); and Group 3 (n=202): standard plus weekly videoconferencing support (S+VCS), hosted by 1 trained facilitator. Participants accessed the intervention, including the questionnaire, on a Web-based learning management system or through a mobile app. The questionnaire, administered at pre- and postintervention, contained self-reported measures of mental well-being, including the "mental health" and "vitality" subscales from the Short Form Health Survey-36, Depression Anxiety and Stress Scale-21, Diener Satisfaction With Life Scale (SWLS), and Diener Flourishing Scale. RESULTS:Of 605 potential participants, 458 (S: n=157, S+pSMS: n=163, and S+VCS: n=138) entered the study by completing registration and the preintervention questionnaire. At post intervention, 320 out of 458 participants (69.9%; S: n=103, S+pSMS: n=114, and S+VCS: n=103) completed the questionnaire. Significant within-group improvements were recorded from pre- to postintervention in all groups and in every outcome measure (P?.001). No significant between-group differences were observed for outcomes in any measure: mental health (P=.77), vitality (P=.65), depression (P=.93), anxiety (P=.25), stress (P.57), SWLS (P=.65), and Flourishing Scale (P=.99). Adherence was not significantly different between groups for mean videos watched (P=.42) and practical activity engagement (P=.71). Participation in videoconference support sessions (VCSSs) was low; 37 out of 103 (35.9%) participants did not attend any VCSSs, and only 19 out of 103 (18.4%) attended 7 or more out of 10 sessions. Stratification within the S+VCS group revealed that those who attended 7 or more VCSSs experienced significantly greater improvements in the domains of mental health (P=.006; d=0.71), vitality (P=.005; d=0.73), depression (P=.04; d=0.54), and life satisfaction (P=.046; d=0.50) compared with participants who attended less than 7. CONCLUSIONS:A Web- and mobile app-based mental health promotion intervention enhanced domains of mental well-being among a healthy cohort, irrespective of human support. Low attendance at VCSSs hindered the ability to make meaningful between-group comparisons. Supplementing the intervention with VCSSs might improve outcomes when attendance is optimized. TRIAL REGISTRATION:Australian New Zealand Clinical Trials Registry (ANZCTR): 12619001009101; http://www.anzctr.org.au/ACTRN12619001009101.aspx.