 Methods: 260 GPs will recruit 2600 hypertensive patients with indication to pharmacological treatment and randomise them to starting treatment with chlortalidone 12.5 to 25 mg daily, 1300 pts or a GP decided single drug excluding thiazides or combination therapy at highest tolerated dose. In both groups any other class of antihypertensive drugs can be added over time in order to achieve blood pressure control 14090 mmHg. Follow-up will last 2 years. Blood sample and urine analyses, carotid and cardiac ultrasound will be performed at baseline and scheduled time points. Genotyping will be performed by sequencing. Data will be collected and stored using a web based centralized Case Report Form CRF Expected results: Results will highlight whether a follow-up strategy based on tight cooperation between GPs and HT specialists can allow the use of thiazides as first line antihypertensive therapy without any negative effect on persistence, adherence and efficacy of the treatment. These data can be used to reduce total burden of the Health Care System in HT by replacing more expensive drugs with diuretics in the 50 of hypertensive patients, who do not receive this class of drugs. Furthermore, the pharmacogenetic approach may clarify the pathophysiological mechanisms of drug-induced metabolic side effects 