Differences in eligibility criteria and intervention characteristics have limited the generalizability of findings from studies of worksite translations of the National Diabetes Prevention Program (DPP). The objective of our study was to identify factors associated with achievement of the DPP's 5% weight-loss goal in the Vanderbilt University Medical Center (VUMC) Faculty and Staff Health and Wellness DPP from 2014 to 2017.We analyzed data from a DPP worksite translation that adhered to national standards for program quality and intervention fidelity. We compared baseline characteristics and program metrics for participants who did and did not achieve the program's 5% weight-loss goal, and we developed a multivariable logistic regression model to identify independent predictors of achieving this goal.Of the 165 employees enrolled in the DPP from 2014 to 2017, 43.6% (n = 72) met the 5% weight-loss goal. Mean (standard deviation) percentage weight loss for the program was 5.2% (6.0%), or 4.8 (6.0) kg. The median (interquartile range) body mass index at baseline was lower among participants who achieved the 5% weight-loss goal than among those who did not (31.6 [29.4-37.4] vs 34.7 [31.5-39.2], P = .009), and participants who achieved the goal reported more physical activity minutes per week (166.0 [135.2-223.0] min vs 128.5 [83.2-169.8] min, P < .001). Session attendance was greater for participants achieving the 5% weight-loss goal (23 [21-25]) sessions vs 18 [12-21] sessions, P < .001). In the adjusted analysis, physical activity and session attendance remained significant predictors of achieving the 5% weight-loss goal.Session attendance and physical activity independently predicted achievement of the 5% weight-loss goal in this worksite translation of the DPP. Strategies designed to improve these metrics may increase DPP success rates.