Background. Guidelines for screening and subsequent treatment of hypertension vary widely between countries. Part of this variation can be attributed to systematic differences between populations, but little is known about the way in which guidelines should be targeted to the population of interest. Optimal guidelines should have high yield and low complexity. The goal is to fit procedures for screening and subsequent treatment of hypertension optimally to a specific population. Methods. Simulation study on individual cardiovascular risk profiles, with drug treatment altering the 10-year cardiovascular risk. The analysis compares the consequences of various screening and treatment alternatives. The reference scenario consists of the Dutch hypertension guidelines for primary care. A representative sample of the Dutch population aged 20 years and older is taken as the target. Main outcome measures include incidence, quality-adjusted life years won, number needed to screen, and costs (prevention, morbidity, and mortality). The discount rate is 4%. Results. Strict adherence to the current hypertension guidelines saves costs (i.e., the total prevention costs are less than the costs of prevented morbidity and mortality). The following changes increase its cost-effectiveness: use of lower blood pressure levels for screening and treatment, reduction of the number of screens from 5 to 3, and active call-up of high-risk patients. The adherence to guidelines has a large influence on actual cost-effectiveness achieved in practice. Conclusions. Appropriate targeting of hypertension guidelines to a population and critical appraisal of the entire screening procedure can enhance cost-effectiveness.