The interaction of the PPARγ Pro12Ala polymorphism with diabetes and cardiovascular risk is controversial. We studied 173 women and 309 men in the observational CARDIPP trial in which determination of left ventricular mass, carotid intima-media thickness (IMT) and pulse wave velocity (PWV) were performed. Blood pressures were measured with 24-h ambulatory technique (ABP). Heterozygotes and homozygotes of Ala were defined as Ala in the analyses. Men with Ala-isoform displayed higher waist circumference (Ala: 107 ± 14 cm, Pro: 104 ± 11 cm, p = 0.045) and body weight (Ala: 95.7 ± 18 kg, Pro: 91.6 ± 14 kg, p = 0.042) than Pro-homozygotes. Men with ALA-isoform also showed higher systolic ABP levels (Ala: 134 ± 15 mmHg, Pro: 130 ± 14 mmHg, p = 0.004), whereas left ventricular mass index, IMT and PWV were unrelated to isoforms. In contrast, carotid-radial PWV was lower in women with the Ala-isoform (Ala: 7.9 ± 1.0 m/s, Pro: 8.5 ± 1.3 m/s, p = 0.01) and levels of apolipoprotein A1 were higher (Ala: 1.43 ± 0.27 g/l, Pro: 1.35 ± 0.17 g/l, p = 0.03). In conclusion, we found that men with type 2 diabetes having the Ala-isoform of PPARγ Pro12Ala had an unfavorable cardiovascular risk profile, whereas women with this isoform had lower carotid-radial PWV and higher apolipoprotein A1 levels suggesting a beneficial prognosis. These differences according to gender of the ALA isoform in type 2 diabetes deserve further attention.