Lifestyle interventions are effective, but those delivered via in-person group meetings have poor scalability and reach. Research is needed to establish if remotely delivered lifestyle interventions are non-inferior to in-person delivered lifestyle interventions. We conducted a randomized non-inferiority trial (N = 329) to compare a lifestyle intervention delivered remotely and asynchronously via an online social network (Get Social condition) to one delivered via in-person groups (Traditional condition). We hypothesized that the Get Social condition would result in a mean percent weight loss at 12 months that was not inferior to the Traditional condition. Additional outcomes included intervention delivery costs per pound lost and acceptability (e.g., convenience, support, modality preferences). At 12 months, no significant difference in percent weight change was observed between the Get Social and Traditional conditions (2.7% vs. 3.7%, p = 0.17) however, criteria for non-inferiority were not met. The Get Social condition costs $21.45 per pound lost versus $26.24 for the Traditional condition. A greater percentage of Get Social condition participants rated participation as convenient (65% vs 44%; p = 0.001). Results revealed a remotely-delivered asynchronous lifestyle intervention resulted in slightly less weight loss than an in-person version but may be more economical and convenient. ClinicalTrials.gov NCT02646618; https://clinicaltrials.gov/ct2/show/NCT02646618 .