Background: The use of Web-based apps to promote a healthy lifestyle is increasing, although most of these programs were not assessed using suitable epidemiological methods. We evaluated the effectiveness of a newly developed Web-based app in promoting a healthy lifestyle and educating adults on such lifestyles. We also analyzed predictors for success in acquiring and maintaining a healthy lifestyle. Objective: Our aim was to compare people receiving a new Web-based app with people who got an introductory lecture alone on healthy lifestyle, weight change, nutritional knowledge, and physical activity, and to identify predictors of success for maintaining a healthy lifestyle. Methods: Subjects were recruited from the community and were randomized into intervention and control groups. The intervention subjects received access to the app without any face-to-face support; the control subjects continued their standard lifestyle. Measurements were taken by the researcher at baseline and after 14 weeks and included weight and waist circumference. Nutritional knowledge, diet quality, and physical activity duration were obtained using online questionnaires. The new Web-based app was developed based on current US Department of Agriculture and Israel Ministry of Health recommendations for healthy lifestyle. The app provides tools for monitoring diet and physical activity while instructing and encouraging healthy diet and physical activity. Results: Out of 99 subjects who were randomized into app and control groups, 85 participants (86%) completed the study, 56 in the intervention and 29 in the control group. The mean age was 47.9 (SD 12.3) years, and mean Body Mass Index was 26.2 (SD 3.9). Among the intervention group only, frequency of app use was 2.7 (SD 1.9) days/week. The mean change in physical activity was 63 (SD 20.8) minutes in the app group and -30 (SD 27.5) minutes in the control group (P=.02). The mean weight change was -1.44 (SD 0.4) kg in the app group and -0.128 (SD 0.36) kg in the control group (P=.03). Knowledge score increased significantly in the app group, 76 (SD 7.5) to 79 (SD 8.7) at the end of the study (P=.04) compared with the control group. Diet quality score also increased significantly at the end of the study, from 67 (SD 9.8) to 71 (SD 7.6; P<.001) in contrast to the control group. Success score (represents the success in maintaining healthy lifestyle) was higher among the app group (68%) compared with 36% in the control group (P<.001). The app frequency of use was significantly related to a higher success score (P<.001). Conclusions: We showed a positive impact of a newly developed Web-based app on lifestyle indicators during an intervention of 14 weeks. These results are promising in the app's potential to promote a healthy lifestyle, although larger and longer duration studies are needed to achieve more definitive conclusions. Trial Registration: Clinicaltrial.gov number: NCT01913496; http://www.clinicaltrials.gov/ct2/show/NCT01913496 (Archived by WebCite at http://www.webcitation.org/6WSTUEPuJ).