BACKGROUND: We sought to investigate the single and combined effect of Mediterranean diet, being physically active, moderate alcohol use, and non-smoking on clinical status of 150 elderly people from Cyprus. METHODS: The study comprises individuals enrolled in surveys from Greece and Cyprus. This work includes 53 apparently men and 97 women, aged 65 to 100 years, from various areas of Cyprus. The cohort study was conducted between 2004 and 2005. A diet score that assesses the inherent characteristics of the Mediterranean diet was developed (range 0-55) and then a healthy index was calculated that evaluated four lifestyle habits (range 0-4), i.e. non-smoking, alcohol intake, physical activity and adherence to the Mediterranean diet (i.e. above the median of the score). RESULTS: 65% participants had hypercholesterolemia (total serum cholesterol > 200 mg/dl or use of lipid lowering agents). Moreover, 32% of the participants reported physically active, 5% reported smoking habits and 4% that they have stopped smoking during the past decade, while 8% reported alcohol drinking. A positive association was observed between prevalence of hypercholesterolemia and smoking habits (odds ratio = 4.3, p = 0.03), while an inverse association was observed between hypercholesterolemia, alcohol drinking (odds ratio = 0.3, p = 0.04) and adherence to a Mediterranean diet (odds ratio = 0.77, p = 0.02), controlled for age, sex, and other factors. CONCLUSION: Adherence to a Mediterranean diet and healthful lifestyle is associated with reduced odds of having hypercholesterolemia among elderly people.