The prevalence and early onset of mental and emotional health problems for children and adolescents suggest an urgent need to explore the potential of preventive intervention programs to strengthen the emotional well-being of youth and insulate them from the harmful effects of stress and other risk factors of daily life. A small but growing base of research shows that mindfulness-based interventions with children and adolescents demonstrate treatment feasibility and acceptability, with encouraging findings in emotional and cognitive well-being, and externalizing behaviors. Mindfulness is the ability to focus one's attention on internal and external experiences as they take place in the present moment, with an attitude of kindness and curiosity. Mindfulness helps individuals to be more accepting and at ease with whatever thoughts, feelings, and bodily sensations arise. When youth are able to simply observe and respond compassionately to their thoughts and impulses without being attached to or pulled by them, they can make choices that are not limited by their habitual emotional reactions. As the research base is still emerging, only a handful of studies have explored mindfulness-based interventions in educational settings; applications of mindfulness have yet to be tested with youth from disadvantaged backgrounds. No studies have empirically evaluated a mindfulness course with middle school students in a classroom setting, or with youth facing homelessness. The purpose of the current study was to evaluate the feasibility, acceptability, and effectiveness of an 8-week mindfulness course in middles school classrooms. A quasi-experimental design with a non-equivalent comparison group of waitlisted students was used to measure student reported changes over time in the domains of acceptance and mindfulness, psychological inflexibility, and self-compassion. Two treatment groups, composed of students attending a traditional middle school (n=38) and with students attending a specialized school serving homeless youth (n=18) were assessed at pre- and posttest. Participants completed a post-course evaluation questionnaire to illustrate their satisfaction and responses to the mindfulness course and how they may have applied mindfulness skills in their daily lives. The first treatment group improved significantly in the domain of psychological acceptance and mindfulness from baseline to post-intervention and in comparison to the comparison group. Both treatment groups experienced improved changes in psychological inflexibility in relation to the comparison group, though the findings were not significant. Highly positive student evaluations and high course completion rates indicated that the mindfulness course was acceptable to both treatment groups and feasibly implemented in their school classrooms. Furthermore, the mindfulness skills were applied in various domains of their daily lives, and led to improved sense of well-being, reduced stress, management of difficult emotions, and improved interpersonal dynamics. The study's findings and clinical observations suggest that quality instructor training, teacher support for classroom behavior management, and class size may be important variables that impact the effectiveness of a mindfulness course for students. Future studies may be enticed by the qualitative results to more objectively explore the effects of a mindfulness course upon levels of stress, anger and aggression, overall quality of life in youth, and overall academic performance.