Background: Digital health interventions are increasingly used to handle and promote positive health behaviors. Clinical measures are often used, and a certain precision is essential for digital health interventions to have an effect. Only few studies have compared clinically measured weights with self-reported weights. No study has examined the validity of self-reported weight from a mobile app used in a tailored weight loss intervention. Objective: The aim of this study was to analyze the agreement between clinically measured weight and self-reported weight collected from a mobile health lifestyle coaching program during a 12-month weight loss intervention for obese patients with and without type 2 diabetes. The secondary aim was to investigate the determinants for possible discrepancies between clinically measured and self-reported weights of these patients with different demographic and lifestyle characteristics and achievements of weight loss goals. Methods: Weight registrations were collected from participants (N=104) in a Danish randomized controlled trial examining the effect of a digital lifestyle intervention on weight loss among obese patients with and without type 2 diabetes. Data were collected at baseline and after 6 and 12 months. Self-reported weight was measured at home and registered in the app. Results: Self-reported body weight was lower than the weight measured in the clinic after 6 months by 1.03 kg (95% CI 1.01-1.05; P<.001) and after 12 months also by 1.03 kg (95% CI 0.99-1.04; P<.001). After 6 months, baseline weight and BMI were associated with a discrepancy of 0.03 kg (95% CI 0.01-0.04; P=.01) and 0.09 kg (95% CI 0.02-0.17; P=.02) per increment of 1 kg and 1 kg/m², respectively, between clinically measured weight and self-reported weight. Weight change during the first 6 months was also associated with a difference of 0.1 kg (95% CI 0.04-0.01; P<.001) per kilogram of difference in weight between clinically measured weight and self-reported weight. Participants who did not achieve the 5% weight loss goal underestimated their weight by 0.79 kg (95% CI 0.34-1.23) at 6 months. After 12 months, only baseline weight was associated with a discrepancy of 0.03 kg (95% CI 0.01-0.05; P=.02) per increment of kilogram between clinically measured weight and self-reported weight. None of the other factors showed any significant discrepancy after 12 months. Conclusions: Self-reported weight obtained from mobile health is a valid method for collecting anthropometric measurements.