BACKGROUND/PURPOSE: This study examined a stress-coping model to assess whether baseline antecedent variables predicted subsequent appraisal and how that appraisal predicted coping and quality of life for prostate cancer patients and their spouses. METHODS: In a sample of 121 prostate cancer patient/spouse dyads, we assessed baseline antecedent variables (self-efficacy, current concerns, age, socioeconomic status, social support, communication, symptoms, phase of illness), 4-month follow-up appraisal (negative appraisal, hopelessness, uncertainty), and 8-month follow-up coping and mental and physical quality of life. Patients and spouses were assessed in a single integrated path model using structural equation modeling. RESULTS: The stress-coping model accounted for a significant amount of variance in mental and physical quality of life at 8 months for patients (40% and 34%, respectively) and spouses (43% and 24%, respectively). Appraisal mediated the effect of several antecedent variables on quality of life. In addition, several partner effects (e.g., spouse variables influencing patient outcomes) were found. CONCLUSIONS: Prostate cancer patients need interventions that assist them to manage the effects of their disease. The stress-coping model suggests skills in several areas that could be improved. Programs need to include spouses because they also are negatively affected by the disease and can influence patient outcomes.