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Background The use of the Internet has the potential to increase access to evidence-based mental health services for a far-reaching population at a low cost. However, low take-up rates in routine care indicate that barriers for implementing Internet-based interventions have not yet been fully identified. Objective The aim of this study was to evaluate the preference for Internet-based psychological interventions as compared to treatment delivered face to face among individuals without past or current use of mental health treatment delivered online. A further aim was to investigate predictors of treatment preference and to complement the quantitative analyses with qualitative data about the perceived advantages and disadvantages of Internet-based interventions. Methods Two convenience samples were used. Sample 1 was recruited in an occupational setting (n=231) and Sample 2 consisted of individuals previously treated for cancer (n=208). Data were collected using a paper-and-pencil survey and analyzed using mixed methods. Results The preference for Internet-based psychological interventions was low in both Sample 1 (6.5%) and Sample 2 (2.6%). Most participants preferred psychological interventions delivered face to face. Use of the Internet to search for and read health-related information was a significant predictor of treatment preference in both Sample 1 (odds ratio [OR] 2.82, 95% CI 1.18-6.75) and Sample 2 (OR 3.52, 95% CI 1.33-9.29). Being born outside of Sweden was a significant predictor of preference for Internet-based interventions, but only in Sample 2 (OR 6.24, 95% CI 1.29-30.16). Similar advantages and disadvantages were mentioned in both samples. Perceived advantages of Internet-based interventions included flexibility regarding time and location, low effort, accessibility, anonymity, credibility, user empowerment, and improved communication between therapist and client. Perceived disadvantages included anonymity, low credibility, impoverished communication between therapist and client, fear of negative side effects, requirements of computer literacy, and concerns about confidentiality. Conclusions Internet-based interventions were reported as the preferred choice by a minority of participants. The results suggest that Internet-based interventions have specific advantages that may facilitate help-seeking among some individuals and some disadvantages that may restrict its use. Initiatives to increase treatment acceptability may benefit from addressing the advantages and disadvantages reported in this study.