Background: Weight loss results in losses of fat mass and fat-free mass/lean body mass loss with accompanying high recidivism and weight regain. Prior studies demonstrated that most weight regain is in the fat mass compartment; however, comprehensive studies utilizing meta-analytical methodologies are need. Therefore, we aimed to synthesize data from randomized controlled weight-loss trials using direct measures of body composition to determine the implications for body composition during weight regain. Methods: The objectives of this systematic review and meta-analysis were to (1) systematically summarize data for body composition during periods of follow-up after weight loss in adults, (2) conduct meta-analyses for body compositional changes during follow-up periods ≥ 6 months, following weight-loss interventions ≥ 12 weeks, and (3) explore potential moderators of weight regain. Embase, PubMed, Scopus, and CINAHL were searched through June 2025. Inclusion criteria comprised randomized controlled trials directly quantifying body composition changes after weight-loss interventions lasting ≥ 12-weeks with ≥ 6-months follow-up. Trial Registration: PROSPERO CRD420251046692. Findings: Thirty-four studies including 4024 participants (female n = 2670) were included· After completion of the weight-loss intervention, body mass (mean difference (MD) 2·99 kg, 95% CI 1·93 to 4·05; p < 0·001) and fat mass (MD 2·56 kg, 95% CI 1·74 to 3·37; p < 0·001) significantly increased at follow-up. No regain was observed for fat-free mass (MD 0·27, 95% CI -0·06 to 0·61; p = 0·11) or lean body mass (MD 0·18, 95% CI -0·15 to 0·50; p = 0·25). Intervention type and follow-up time were not related to outcomes. Interpretation: Weight regain following weight-loss intervention primarily reflects FM recovery, not fat-free mass or lean body mass. The findings of this systematic review and meta-analyses may have implications for cardiometabolic health and physical function following weight loss and weight regain.