Aims: This study was designed to analyse the association between adherence to guidelines for rational drug use and surrogate outcome markers for hypertension, diabetes and hypercholesterolaemia. Methods: The study used a cross-sectional ecological design. Data from dispensed prescriptions and medical records were analysed from 24 primary healthcare centres with a combined registered population of 330,000 patients in 2006. Guideline adherence was determined calculating the proportion of the prescribed volume of antidiabetic agents, antihypertensives and lipid-lowering agents representing the 14 different drugs included in the guidelines for these three areas. Patient outcome was assessed using surrogate marker data on HbA1C, blood pressure (BP) and s-cholesterol. The association between the guidelines adherence and outcomes measures was analysed by logistic regression. Results: The proportion of guideline antidiabetic drugs in relation to all antidiabetic drugs prescribed varied between 80% and 97% among the practices, the ratio of angiotensin converting enzyme (ACE)-inhibitors to all renin-angiotensin drugs 40-77% and the ratio of simvastatin to all statins 58-90%. The proportion of patients reaching targets for HbA1C, BP and s-cholesterol varied between 34% and 66%, 36% and 57% and 46% and 71% respectively. No significant associations were found between adherence to the guidelines and outcome. The expenditures for antihypertensives and lipid-lowering drugs could potentially be reduced by 10% and 50% respectively if all practices adhered to the guidelines as the top performing practices. Conclusion: A substantial amount of money can be saved in primary care without compromising the quality of care by using recommended first-line drugs for the treatment diabetes, hypertension and hypercholesterolaemia.