Parenting is a stressful endeavor that can be even more difficult for parents of individuals with Autism Spectrum Disorders (ASD). Autism Spectrum Disorder (ASD) has become increasingly prevalent over the past 15 years, which has baffled researchers and frustrated parents. Respite can be important to help alleviate stress for parents of individuals with ASD, and serve as a break for them from the demands of parenting. The present study utilized a mixed methods design to study the effect of respite on caregiver well-being. Using quantitative data, the study examined the effects of a respite cruise vacation organized by a travel group called Autism on the Seas on various indices of well-being among 20 parents of children with ASD. Parents provided survey responses prior to the cruise (pre-cruise measure) and three months after the cruise (post-cruise measure). Variables included caregiver stress, caregiver self-efficiency, caregiver social network and family quality of life. It was hypothesized that the Autism on the Seas respite vacation experience would be related to increased well-being among caregivers, specifically decreased caregiver reports of stress, increased caregiver reports of social network, increased caregiver reports of family quality of life, and increased caregiver report of self-efficacy. The quantitative study found significant associations among the well-being variables, however no statistical difference between the caregivers’ reports of well-being on pre and post cruise measures. The qualitative component of the study aimed to describe perceptions of respite, barriers to respite-utilization, and aspects of respite that caregivers of children with ASD described as most beneficial. Six couples and one single father participated in the qualitative component of the study. Interview transcriptions were all analyzed through open coding and then axial coding to find data trends and themes. It was hypothesized that respite would bring positive experiences to caregivers, allowing caregivers to take time to maintain their own well-being psychologically and physically. The qualitative study revealed the themes of the centrality of trusted caregivers to parent’s willingness to accept respite, limited social networks of parent with children with ASD, and both caregiver well-being and child well-being and severity of ASD as important to parents’ use of respite programs such that parents of children with more severe ASD reported more trouble accessing respite care. Together, the study points to the need for future studies to investigate a broad range of types of respite programs for individuals with ASD and their families.