The present mixed-methods study examined how 19 experienced change leaders cope with ambiguity during transformational organizational change and whether mindfulness helps them do that. Study findings indicated that practitioners react in varying ways to ambiguity and employees generally react negatively. Change leaders rely on personal coping and project initiation strategies, ongoing guidance and support, agile and action-oriented approaches, courageous and bold leadership, and trust in their process to manage ambiguity for themselves. To help others deal with ambiguity, change leaders repeatedly articulate the change vision and direction and demonstrate confident, strong change leadership. Mindfulness appears to enhance leaders’ abilities to interact with others, maintain perspective, and attune with others’ emotional states. Mindful change leaders appear to more frequently practice self-awareness and self-care, seek professional advice and assistance, and exercise an agile, action-oriented approach to leading change as ambiguity coping mechanisms.