Abstract Reducing ≥5% of body weight can decrease the risk of developing chronic diseases in adults with excess weight. Although Intensive Lifestyle Interventions (ILIs) that include cognitive-behavioral techniques to improve physical activity and eating habits are the best approach for losing weight, the failure to retain participants is a barrier to their successful implementation. We aimed to investigate the factors influencing adults to drop out of ILIs for weight loss at six months. We conducted retrospective multiple logistic regression analysis of 268 participants with excess weight (body mass index ≥ 25 kg/m2) from a multicenter study (n = 237, in-person ILI in five clinics, delivered by nutrition interns), and a randomized controlled trial (n = 31, one online ILI, delivered by a master’s degree student). The same research team conducted both studies in Northern Mexico, using the same intervention components, and identical instruments and techniques to collect the data. We found that older participants (≥50 years) were less likely to drop out of the ILI for weight loss compared to participants <35 years old (OR = 0.34, 95% CI = 0.16–0.70). For each unit increase in the bodily pain scale of the SF-36 (less perceived pain), the risk of dropping out decreased by 2% (OR = 0.98, 95% CI = 0.97, 0.996), while a change in the interventionist during the 6-month intervention more than doubled the risk of dropping out (OR 2.25, 95% CI = 1.23–4.14). Retention in ILIs may be improved by ensuring that the same interventionist remains during the six-month intervention. In addition, ILIs may need further tailoring for younger ages and for participants with higher perceived pain.