Background: Previous experience may affect further coping with illness. The aim of the current study was to evaluate the association between prior cancer of spouse with mortality following a personal diagnosis of cancer. Methods: A historical prospective study, with cohort inception and baseline measurement of people participating in the Central Bureau of Statistics 1995 census, was designed. Cancer incidence was ascertained through the Israel Cancer Registry and followed up until 2011. Multivariate Cox proportional hazards models were used to assess hazard ratios for mortality among study subjects following cancer of their spouse, while controlling for age, sex, marital status and ethnicity. In order to exclude lead time bias and smoking effect, further analyses which restricted to stage IV cancers and models which excluded smoking associated cancers (lung, head and neck, renal, and bladder cancers) were carried. Results: A total of 133,550 cases of cancer and 61,048 deaths were reported during the study period. The effect on mortality was mediated by spouse’s survival at the time of self-diagnosis; mortality of spouse, at the time of personal diagnosis of cancer was associated with increased risk for death (HR=1.07, 95%CI: 1.02-1.12) compared with reduced risk of personal mortality following a diagnosis of cancer in spouse whose was alive at time of diagnosis (HR=0.90, 95%CI: 0.87-0.94). The gender effect was more prominent in stage IV patients; only males were susceptible to the negative effect after spouse mortality (HR=1.20, 95%CI: 1.06-1.36) while the protective effect of a spouse who was alive at time of self-diagnosis was significant only among females (HR=0.79, 95%CI: 0.71-0.89). These results were similar in the models which included only non-smoking associated cancers. Conclusions: Mortality followed cancer diagnosis is affected by prior diagnosis of cancer among the spouse. This effect is influenced by the survival of the spouse at the time of cancer diagnosis and gender.