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Prospective studies have reported that positive psychological well-being is associated with a reduced risk of cardiovascular disease. Direct psychobiological processes have been implicated in this association. It is unclear to what extent well-being predicts health outcomes independently of chronic stressors, such as job strain. This thesis explores associations between well-being, job strain and outcomes relevant to cardiovascular disease in four empirical studies. Two biomarkers are investigated: cortisol, a neuroendocrine marker, and blood pressure. In study one, higher positive emotions over one week predicted lower reported stress during a standardised laboratory mental stress task, lower cortisol responses and faster blood pressure recovery. In study two, cross-sectional analyses of employee surveys indicated that low positive affect could mediate associations between job strain and fatigue, but reverse associations could not be discounted. Study three showed that job strain predicted heightened evening cortisol and a flatter diurnal rhythm in shift workers. Positive affect was not associated with cortisol. The hypothesis emerged that intervening to increase well-being might reduce perceived job strain and associated physiological activation. Study four tested this hypothesis in healthy workers using a mindfulness meditation smartphone application to promote well-being. The intervention was associated with increased well-being, reduced job strain and a trend for lower blood pressure after eight weeks. Decreased negative affect, not positive affect, predicted blood pressure declines. Changes in hair cortisol concentration were not associated with the intervention or psychological outcomes. Well-being appears to predict favourable cognitive appraisals of the work environment. Frequent positive emotions may reduce autonomic activation directly or via a reduction in negative emotion. Intervention findings suggested that self-guided mindfulness meditation practice enhanced well-being in the short term but effects on blood pressure and cortisol were inconclusive. Further research to examine longer term effects on psychological and biological outcomes is warranted to determine whether mindfulness-based therapies could play a role in cardiovascular disease prevention.