Increased blood pressure variability (BPV) contributes to end-organ damage, cardiovascular events and mortality associated with hypertension. In a cohort of 2780 hypertensive patients treated by either calcium channel blockers (CCBs), diuretics, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) or β-blockers alone or in combination, we compared indices of short-term BPV according to the different treatments. Short-term BPV was calculated as the standard deviation (s.d.) of 24 h, daytime or nighttime systolic blood pressure and diastolic blood pressure (SBP and DBP). Short-term BPV was compared between patients treated with a given antihypertensive class of interest (alone or in combination) and those not treated with this class, after controlling for ambulatory average blood pressure, heart rate, age, gender, propensity scores and carotid-femoral pulse wave velocity. Patients treated with CCBs (n=1247) or diuretics (n=1486) alone, or in addition to other drugs had significant lower s.d. of 24-h SBP compared with those not treated with these classes (mean differences in s.d. -0.50±0.50 mm Hg, P=0.001 and -0.17±0.15 mm Hg, P=0.05, respectively). There was no significant difference regarding treatment with or without ARBs, ACEIs and β-blockers. The combinations of CCBs with diuretics or ARBs on top of other treatments resulted in a lower 24-h SBP variability (mean differences in s.d. -0.43±0.17 mm Hg, P=0.02 and -0.44±0.19 mm Hg, P=0.005 vs. other combination uses, respectively). Antihypertensive drug classes have differential effects on short-term BPV with a greater reduction in patients treated with CCBs and diuretics. The combinations of CCBs with diuretics may be the most efficient treatments in lowering BPV.