Introduction: Employers are instituting employee wellness programs that include educational, lifestyle coaching, and weight and other condition management components to address obesity-related issues in the workplace. However, the findings of such wellness initiatives have been mixed. The purpose of this exploratory study is to determine whether the readiness for change measures are important predictors of weight loss in an employee wellness program. Methods: Retrospective data analysis of an employee wellness program conducted in the United States was conducted using data collected between 2014 and 2015 for people with BMI ≥ 30. These participants were assigned to one of two subprograms: weight management or condition management. We assessed the weight change within each program. Further, the relationship between weight change and readiness for change variables for weight, diet, and physical activity were examined by applying multiple linear regression and logistic regression models. The multivariable model included subprogram; gender; age; systolic and diastolic blood pressure; risk factor count; readiness for change for weight, activity, and diet; and stress level as covariates. Results: There were 209 participants in the weight management program and 243 participants in the condition management program who met the criteria for obesity, resulting in a final sample of 452 participants. On average, the weight change for these participants was −0.28 pounds (SD = 15.55) and there was no statistical difference between the weight change in the two programs. When compared to the reference group (maintenance), participants at the action stage of physical activity, on average, lost weight (b = −4.59, p = 0.02). Likewise, participants at the pre-contemplation stage of physical activity lost weight when compared to the maintenance group (b = −26.24, p = 0.000). Participants at the pre-contemplation stage of physical activity had higher odds of achieving at least 5% weight loss than participants at the maintenance stage (OR = 5.80, p = 0.053). Conclusion: Readiness for change for activity may be a predictor of weight change, and may predict the likelihood of achieving clinically significant weight loss. These findings can assist in targeting subjects for participation in such programs. The findings regarding the relationship between readiness for change and weight loss are counterintuitive, and further research is warranted in this area.