BACKGROUND: Weight change after a breast cancer diagnosis has been linked to lower survival. To further understand effects of postdiagnostic weight variation on survival, we examined the relationship by comorbid status and initial body mass index (BMI). METHODS: The current analysis included 12,915 patients with breast cancer diagnosed between 1990 and 2006 with stage I-III tumors from four prospective cohorts in the United States and China. HRs and 95% confidence intervals (CI) representing the associations of five weight change categories [within <5% (reference); 5%-<10% and >/=10% loss and gain] with mortality were estimated using Cox proportional hazards models. RESULTS: Mean weight change was 1.6 kg. About 14.7% women lost and 34.7% gained weight. Weight stability in the early years postdiagnosis was associated with the lowest overall mortality risk. Weight loss >/=10% was related to a 40% increased risk of death (HR, 1.41; 95% CI, 1.14-1.75) in the United States and over three times the risk of death (HR, 3.25; 95% CI: 2.24, 4.73) in Shanghai. This association varied by prediagnosis BMI, and in the United States, lower survival was seen for women who lost weight and had comorbid conditions. Weight gain >/=10% was associated with a nonsignificant increased risk of death. CONCLUSIONS: Prevention of excessive weight gain is a valid public health goal for breast cancer survivors. Although intentionality of weight loss could not be determined, women with comorbid conditions may be particularly at risk of weight loss and mortality. IMPACT: Weight control strategies for breast cancer survivors should be personalized to the individual’s medical history.