To develop an evidence-based compassion fatigue program and evaluate its impact on nurse-reported burnout, secondary traumatic stress, and compassion satisfaction, as well as correlated factors of resilience and coping behaviors. The quality improvement pilot program was conducted with 59 nurses on a 20-bed subspecialty pediatric oncology unit at the St. Jude Children's Research Hospital in Memphis, Tennessee. Validated measures of compassion fatigue and satisfaction (Professional Quality of Life Scale V [ProQOLV]), coping (Brief COPE), and resilience (Connor-Davidson Resilience Scale-2) were evaluated preprogram and at two, four, and six months postprogram, with resilience and coping style measured at baseline and at six months postprogram. Secondary traumatic stress scores significantly improved from baseline to four months. Select coping characteristics were significantly correlated with ProQOLV subscale scores. Ongoing organizational support and intervention can reduce compassion fatigue and foster compassion satisfaction among pediatric oncology nurses.