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Understanding teachers’ stress is of critical importance to address the challenges in today’s educational climate. Growing numbers of teachers are reporting high levels of occupational stress, and high levels of teacher turnover are having a negative impact on education quality. Cultivating Awareness and Resilience in Education (CARE for Teachers) is a mindfulness-based professional development program designed to promote teachers’ social and emotional competence and improve the quality of classroom interactions. The efficacy of the program was assessed using a cluster randomized trial design involving 36 urban elementary schools and 224 teachers. The CARE for Teachers program involved 30 hr of in-person training in addition to intersession phone coaching. At both pre- and postintervention, teachers completed self-report measures and assessments of their participating students. Teachers’ classrooms were observed and coded using the Classroom Assessment Scoring System (CLASS). Analyses showed that CARE for Teachers had statistically significant direct positive effects on adaptive emotion regulation, mindfulness, psychological distress, and time urgency. CARE for Teachers also had a statistically significant positive effect on the emotional support domain of the CLASS. The present findings indicate that CARE for Teachers is an effective professional development both for promoting teachers’ social and emotional competence and increasing the quality of their classroom interactions.