BACKGROUND: We examined the influence of the AGTR1 A1166C genotype on the 16-year evolution of pulse wave velocity (PWV) in a middle-aged population. In a cross-sectional study, we reported that the presence of the AGTR1 1166C allele was associated with higher aortic stiffness compared with the AGTR1 1166AA genotype. METHODS: The study was conducted in 259 subjects who underwent 3 health check-ups over 16 years at the Centre IPC-Paris: an initial visit in 1992-1993, an intermediate visit in 1998-1999, and a final visit in 2007-2008. Aortic stiffness was assessed during the 3 visits by measuring carotid-femoral PWV. AGTR1 A1166C polymorphism was assayed by allele-specific oligonucleotide hybridization. RESULTS: AGTR1 1166C allele carriers (AC + CC genotypes) had a 35% more pronounced increase in PWV over this 16-year period when compared with the AGTR1 1166AA subjects (3.01 ± 0.32 vs. 1.92 ± 0.23 m/s; P < 0.001). This increase remained significant after adjustment for age, sex, initial PWV values, and changes in blood pressure (+37%; P < 0.05). The genotype-related differences in PWV were only observed at the last visit (i.e., later in life, after the age of 55 years). The effects of this genotype on PWV were not related to the presence of antihypertensive treatment. CONCLUSIONS: This is the first long-term longitudinal study indicating that AT1 1166C carriers are at increased risk of pronounced arterial stiffening during aging especially after the age of 55.