"Background: Although there are two meta-analyses reporting that happiness is protective of mortality, recent discussion has suggested that this relation may be confounded by baseline Background: Although there are two meta-analyses reporting that happiness is protective of mortality, recent discussion has suggested that this relation may be confounded by baseline health status. Aim: To examine the relation between happiness and mortality by chronic disease health status and whether this relation is consistent over time. Methods: Participants were 7,753 consenting adults, aged 55+, without dementia who completed happiness questions from the Center for Epidemiological Studies Depression (CES-D) scale between 1997-2001, 2002-2005, and/or 2009-2012 as part of the Rotterdam Study. Chronic disease status was defined as the presence of either CVD, cancer and/or diabetes. Events were continuously monitored through medical records. Results: During the 626,647 person-years of observation, there were 3,506 deaths. In the total sample, happiness was protective of mortality at all three time points. However when split by chronic disease status, the relation was only present in participants with chronic disease. The question â€œI felt that I was just as good as other peopleâ€ was consistently protective of mortality, while â€œI felt hopeful about the futureâ€ was protective of mortality at two time points. Although analyses were adjusted for demographic, behavioural, anthropometric, cognitive and functional variables, this relation may be confounded by disease severity. Conclusion: In population-based 55+ year olds with chronic disease, happiness was protective of mortality during 11-years follow-up. Feeling comparable to peers and greater optimism were particularly good predictors. In those without chronic disease, no relations were observed between happiness, optimism, comparison to peers, life enjoyment or life satisfaction with mortality. Key words: Ageing/elderly, Epidemiology, Mental health Key Messages: 1. We observed that happiness prevented death only in those with chronic disease, not in the healthy. 2. Our finding concurs with current discussion suggesting that the relation between happiness and mortality may be confounded by baseline health status. 3. Feeling comparable to peers and greater optimism were particularly good predictors. "