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 Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn.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: Mobile health applications (mHealth apps) may have the potential to promote self-management of people with multiple sclerosis (MS) in everyday life. However, the uptake of MS apps remains poor and little is known about the facilitators and barriers for their efficient utilization, such as technology acceptance. Objective: The aim of this study was to examine the acceptance of mHealth apps for disease-management in the sense of behavioral intentions to use and explore determinants of utilization among people with MS based on the Unified Theory of Acceptance and Use of Technology (UTAUT). Methods: Participants for this Web-based cross-sectional study were recruited Germany-wide with the support of regional MS associations and self-help groups. To identify determinants of intention to use MS apps, a measure based on the UTAUT was adapted with four key determinants (performance-/effort-expectancy, social influence, facilitating conditions) and extended by Intolerance of Uncertainty (IU) and eHealth literacy. Potential influencing effects of both MS and computer self-efficacy as mediators and fatigue as a moderator were analyzed using Hayes' PROCESS macro for SPSS. Results: 98 participants (M age=47.03 years, SD=10.17; 67.3% female, 66/98) with moderate fatigue levels completed the survey. Although most participants (91.9%; 91/98) were daily smartphone users, almost two-thirds (63.3%, 62/98) reported no experience with MS apps. Overall, the acceptance was moderate on average (M=3.11, SD=1.31, min 1 max 5), with lower scores among persons with no experience (P=.04) and higher scores among current users (P<.001). In multiple regression analysis (R2=63% variance explained), performance expectancy (beta=.41) and social influence (beta=.33) were identified as significant predictors of acceptance (all P<.001). Computer self-efficacy was confirmed as a partial mediator in the relationship between IU and acceptance; (indirect effect: B=-.095, 95% CI-0.227,-0.01). Furthermore, a moderated mediation by computer self-efficacy was shown in the relationship between IU and behavioral intentions to use MS apps for low (95% CI -0.42,-0.01) and moderate levels (95% CI -0.27,-0.01) of fatigue. Conclusions: Overall, this exploratory pilot study indicates for the first time that positive expectations about the helpfulness for self-management purposes and social support might be important factors to be considered for improving the acceptance of MS apps among smartphone users with MS. However, given some inconsistent findings, especially regarding the role of effort expectancy and IU and self-efficacy, the conceptual model needs replication with a larger sample of people with MS, varying more in fatigue levels, and a longitudinal assessment of the actual usage of MS apps predicted by acceptance in the sense of behavioral intentions to use. Clinical Trial: not applicable