Arterial hypertension is characterised by increased oxidative stress and inflammation, which are associated with further cardiovascular risk. The aim of our study was to investigate the long-term effects of nebivolol and metoprolol succinate on oxidative stress, and on inflammatory and pro-inflammatory markers in patients with hypertension. Eighty patients with never-treated mild-to-moderate essential hypertension, aged 30-65 years, were randomised to a 5 mg daily dose of nebivolol or a 50-100 mg daily dose of metoprolol succinate. Brachial blood pressure, plasma oxidized LDL (oxLDL), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), fibrinogen, intercellular adhesion molecule-1 (ICAM-1), asymmetric dimethylarginine (ADMA), and urine 8-isoprostane levels were measured before and after 1 year of treatment. Nebivolol and metoprolol reduced equally significantly brachial blood pressure. The oxLDL was significantly reduced in both groups (p < 0.01 and for both drugs), but only nebivolol reduced 8-isoprostanes (p = 0.01). In the metoprolol group, change in oxLDL levels correlated with change in systolic blood pressure (r = 0.45; p < 0.01) and pulse pressure (r = 0.47; p < 0.01). Both metoprolol and nebivolol reduced ICAM-1 (p < 0.01). There was no change in IL-6, hsCRP, fibrinogen, or ADMA levels in either group. These data suggest that in long-term antihypertensive treatment both the cardioselective beta blocker metoprolol succinate and the vasodilating beta blocker nebivolol have inflammation-related effects but only nebivolol has a favourable blood pressure-independent effect on oxidative stress.