The purpose of this multicenter longitudinal randomized controlled trial was to examine the efficacy of self-administered stress management training (SSMT) in improving quality of life and reducing psychological distress among patients receiving cancer chemotherapy. Participants were randomized to SSMT (n = 111) or usual psychosocial care only (n = 109). Mixed linear modeling demonstrated no significant improvements in primary outcome measures; however, participants assigned to SSMT reported using significantly more relaxation techniques (p < 0.0001), showed improvements on emotional adjustment scores, and demonstrated a stabilizing effect on the functional adjustment scores. Findings highlight the usefulness of SSMT in community clinical settings.