Identifying the effects of social and motivational factors is critical to understanding how healthy behaviors, i.e., physical activities, spread in digital therapeutics programs. We evaluated a comprehensive interconnected social network of 254 overweight and obese individuals across 335 days. Daily physical activities, social activities, biomarkers, and biometric measures were available for all subjects. We improved proportional hazards models to characterize the impact of self-motivation, influence, and susceptibility in the spread of physical activities. After 6 months, the YesiWell users increased leisure walking minutes by 164% on average compared with 47% among the control participants (P< 0.05 ). The YesiWell users also lost more weight than the controls (5.2 pounds vs. 1.5 pounds) (P< 0.01 ). Our estimations showed that influence and susceptibility increase with age; relaxed people are 96% more influential than stressed people (P< 0.001 ); obese people are 23% more self-motivated (P< 0.001 ); socially active people are 29% more influential (P< 0.001 ); those who self-characterize as “keep-to-themselves” people have a 79% greater susceptibility (P< 0.001 ). Relaxed people exert the most influence on non-stressed peers at 109% more than baseline (P< 0.001 ). Our findings could enable new and effective personalized behavioral interventions to spread healthy behaviors in next-generation digital therapeutics.