Objectives: The present study was a 2 × 2 factorial randomized controlled trial that examined if a simulation-based empathy enhancement program and a lecture-based education program, together or separately, improved outcomes of family caregivers of people with dementia. Method: A total of 101 participants were randomly assigned to simulation-based education only, lecture-based education only, simulation-based education plus lecture-based education, or treatment as usual. Data were analyzed using a two-way analysis of covariance while controlling for pretest results, kinship, and gender. Results: Statistically significant interaction effects between the simulation program and the lecture program were found in the levels of well-being and helplessness. The lecture program accompanied by the simulation program led to higher level of well-being in terms of happiness and lower level of helplessness than the lecture program alone. Caregivers with the lecture program provided led to less frequent use of dysfunctional coping strategies than those with no lecture program provided. Caregivers with the simulation program provided led to more frequent use of emotion-focused coping strategies than those with no simulation program provided. Conclusions: Findings of the present study support benefits of combined of and separate simulation-based and lecture-based programs on family caregivers of people with dementia in important outcomes affecting quality of care and quality of lives in families of people with dementia. Further studies are needed to identify intervention components that can improve empathy of family caregivers of people with dementia and be embedded into a multicomponent program tailored better to families in different needs.