OBJECTIVES: Workplace wellness programs (WWPs) are of increasing interest globally as employers, insurers and policy makers attempt to grapple with improving employee health while containing health care costs. WWPs are workplace-based programs that incorporate health promotion activities with the goal of improving the health of employees. This research aimed to determine the effectiveness of a comprehensive WWP in reducing prescription drug costs during the first 2 years following program implementation.   METHODS: A quasi-experimental pre-post design was used to assess changes in employees’ prescription drug costs. The analysis examined prescription drug claims of treatment group employees versus control group employees, with 12-month pre-intervention (baseline) and 24-month intervention periods. Differences in differences logistic and generalized linear regression models were used to assess the impact of WWP on the probability of incurring costs and level of prescription drug expenditures, respectively. All regression models controlled for the differences in the baseline prescription drug costs and demographic characteristics of the employees.  RESULTS: After adjusting for baseline differences, the probability of incurring prescription drug expenditures and level of prescription drug costs for WWP participants fell significantly from pre-intervention to post-intervention relative to controls. Estimated prescription drug cost savings were $280 per employee per year. Analysis suggested a $1.86 return for every dollar of investment (ROI) over two years generated by the effect of implementing a comprehensive WWP.  CONCLUSIONS: It appears that comprehensive WWPs in Canada can lead to significant reduction in prescription drug costs and thereby generate a positive return on investment. This positive ROI suggests that WWPs add financial value to Canadian employers that invest in WWPs. To our knowledge, this is the first study of its kind in Canada.