The aim of this systematic review is to answer the question: Is substantial, stable, and long‐term weight loss a viable goal for adults with obesity? To answer this question, we conducted a broad systematic search of non‐surgical and non‐pharmacological obesity treatment studies with the following strict criteria: (a) minimum 3‐year follow‐up, (b) 5% body mass lost, (c) no continued interventions in the follow‐up‐period, (d) prospective design, and (e) less than 30% attrition from the start of the follow‐up period. While the search revealed a very large number of published articles, only eight studies met the inclusion criteria. Several of the nonincluded studies report a majority of participants achieving satisfactory weight loss and little regain, especially among studies with continued interventions during the follow‐up period. In contrast, the eight high‐quality studies included in this study demonstrate a trend of weight regain towards pretreatment baseline. This review concludes that the majority of high‐quality follow‐up treatment studies of individuals with obesity are not successful in maintaining weight loss over time. The results suggest that excess weight can be lost but is likely regained over time, for the majority of participants.