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Subjects with metabolic syndrome (MetS) or obesity have worse arterial stiffness. However, there have been no studies addressing time-sequential changes in pulse wave velocity (PWV) after weight loss and then regaining weight in obese non-diabetic men with MetS.We prospectively enrolled 40 obese, non-diabetic men with MetS undergoing a 3-month weight reduction program. Another 26 lean and healthy men were recruited for comparisons. Oral glucose tolerance test and brachial ankle (ba) PWV were assessed in study subjects. Eighteen obese non-diabetic MetS and 15 lean control subjects had follow-ups at the 60th month.The body weight of obese MetS decreased from 94.8 ± 7.6 to 86.1 ± 9.0 (N = 18, P < .001) after a 3-month weight reduction program but regained gradually thereafter to 93.6 ± 11.6 kg at the 60th month (P < .001 versus 3rd month). baPWV decreased after weight loss slightly (P = .240) while weight regain significantly increased the baPWV (from 3rd month, 1358 ± 168 to 60th month 1539 ± 264 cm/sec, P < .001). Systolic and diastolic blood pressure increments correlated with the increment of baPWV after weight regain. At the 60th month, lean controls (N = 15) had increases in body weight while their baPWV increased non-significantly. The increments of baPWV after weight regain in obese MetS were significantly higher than the increment of baPWV in lean controls after weight gain.In conclusion, regaining body weight after weight reduction worsened arterial stiffness with significant increase of baPWV in obese non-diabetic MetS.