Few studies assessed incidence and determinants of hypertension. We assessed the incidence and determinants of hypertension in a cohort of healthy adults aged 35-75 years living in Lausanne, Switzerland. Baseline data were 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 35-75 developed hypertension. Male gender, history of CVD, increasing age and higher BMI increase the risk of hypertension, while being physically active reduces the risk.