Objective: Selective study dropout limits manifestation and detection of intervention effects and is a major challenge in behavioral intervention studies. Engaging in health-risk behaviors might make individuals especially dropout-vulnerable. Thus, this theory-based study's aim was to identify health-related lifestyle profiles affecting dropout in a web-based physical activity intervention trial targeting older adults. Method: The 12week intervention trial was conducted between 2016 and 2018 in Germany. Baseline lifestyle profiles consisting of self-reported physical activity, sedentary behavior, alcohol consumption, fruit and vegetable intake, nocturnal sleep, and social activity were assessed with questionnaires and investigated in 589 individuals. The risk of study dropout related to health-related lifestyle profile was tested with Poisson regression in 571 individuals (96.9%). Results: Latent profile analysis identified four latent health-related lifestyle profiles: socially inactive (n = 23, 3.9%), slightly unhealthy (n = 449, 75.2%), health-promoting (n = 81, 13.8%), and highly physically active lifestyle (n = 36, 6.1%). Profiles differed significantly by sex, stage of behavior change, and subjective health. Compared with the average of all profiles, statistically significant study dropout adjusted risk ratios (aRR) were 1.91 for the socially inactive lifestyle, and aRR = 0.73 for the slightly unhealthy lifestyle. There were no statistically significant effects for the highly physically active lifestyle (aRR = 0.94) and the healthpromoting lifestyle (aRR = 0.76) on study dropout. Conclusions: This study highlights the relevance of accounting for the correlation between health-related lifestyle profiles and study participation of older adults in physical activity interventions.