BACKGROUND: A Mediterranean dietary pattern is widely recommended for the prevention of chronic disease. We sought to define the most likely effects of the Mediterranean diet on vascular disease and mortality. METHODS: We searched MEDLINE, EMBASE and the Cochrane Central Register without language restriction for randomized controlled trials comparing Mediterranean to control diets. Data on study design, patient characteristics, interventions, follow-up duration, outcomes and adverse events were sought. Individual study relative risks (RR) were pooled to create summary estimates. RESULTS: Six studies with a total of 10950 participants were included. Effects on major vascular events (n = 477), death (n = 693) and vascular deaths (n = 315) were reported for 3, 5 and 4 studies respectively. For one large study (n = 1000) there were serious concerns about the integrity of the data. When data for all studies were combined there was evidence of protection against major vascular events (RR 0.63, 95% confidence interval 0.53-0.75), coronary events (0.65, 0.50-0.85), stroke (0.65, 0.48-0.88) and heart failure (0.30, 0.17-0.56) but not for all-cause mortality (1.00, 0.86-1.15) or cardiovascular mortality (0.90, 0.72-1.11). After the study of concern was excluded the benefit for vascular events (0.69, 0.55-0.86) and stroke (0.66, 0.48-0.92) persisted but apparently positive findings for coronary events (0.73, 0.51-1.05) and heart failure (0.25, 0.05-1.17) disappeared. CONCLUSION: The Mediterranean diet may protect against vascular disease. However, both the quantity and quality of the available evidence is limited and highly variable. Results must be interpreted with caution.