Few studies assessed incidence and determinants of hypertension. We assessed the incidence and determinants of hypertension in a cohort of healthy adults aged 35 to 75 years living in Lausanne, Switzerland. Baseline data was collected from 2003 to 2006. Follow-ups were conducted in 2009-2012 and 2014-2017. Incident hypertension, defined as a systolic BP ≥140 mm Hg or a diastolic BP ≥90 mm Hg or anti-hypertensive medication, was assessed at 1) second follow-up only; 2) first and/or second follow-up. After 10.9 years, incident hypertension was 26.8% (analysis 1, N=3299) and 30.3% (analysis 2, N=3728). After multivariate adjustment, the variables associated with increased hypertension incidence were male gender [incident-rate ratio (IRR) and (95% confidence interval)]: 1.20 (1.07-1.35) and 1.24 (1.13-1.37) for analyses 1 and 2, respectively; increasing age (p for trend <0.001) and body mass index (p for trend <0.001) and history of cardiovascular disease (CVD). Being physically active was negatively associated with incident hypertension: 0.88 (0.78-0.98) and 0.92 (0.83-1.01) for analyses 1 and 2, respectively. Except for male gender, these associations remained after adjusting for baseline BP levels, with incident rate ratios for physical activity of 0.86 (0.77-0.96) and 0.91 (0.83-0.99) for analyses 1 and 2, respectively. No association was found for education, alcohol consumption or smoking status. We conclude that over 10.9 years, between 1/4 and 1/3 of the Swiss population aged 35 to 75 developed hypertension. Male gender, history of CVD, increasing age and higher BMI increase the risk of hypertension, while being physically active reduces the risk.