Aim. - Adiponectin is the most abundant adipokine and may play a key role in the interplay between obesity, inflammation, insulin resistance and the metabolic syndrome (MetS). Thus, this large population-based cohort investigated whether adiponectin at baseline and/or a decrease in adiponectin during follow-up is associated prospectively with the risk of incident MetS. Methods. - Using a prospective study design, the development of MetS was examined in 1134 healthy participants from the community. Plasma adiponectin was measured at study entry and again after a median follow-up of 9.4 years (IQR: 9.2-9.7). During follow-up, 187 participants developed MetS, and 439 presented with at least two components of MetS. Results. - During follow-up, adiponectin decreased in participants who developed MetS, whereas adiponectin was increased in those who did not develop MetS (P < 0.001). Those with low adiponectin levels (quartile 1) at baseline had an increased risk of developing MetS (OR: 2.92, 2.08-6.97; P < 0.001) compared with those with high levels (quartile 4). After adjusting for confounding variables, low adiponectin levels at baseline remained independently associated with MetS (OR: 2.24, 1.11-4.52; P = 0.017). Similarly, participants with a decrease in adiponectin during follow-up also had an increased risk of MetS (OR: 2.96, 2.09-4.18; P < 0.001). This association persisted after multivariable adjustments, including for baseline adiponectin (OR: 4.37, 2.77-6.97; P < 0.001). Finally, adiponectin levels at follow-up were inversely associated with an increase in the number of components of MetS (P <0.001); geometric mean adiponectin levels were 9.5 mg/L (95% CI: 9.0-10.0) for participants with no components vs 7.0 mg/L (95% CI: 6.3-7.9) for those with four to five components. Conclusions/interpretation. - Low plasma adiponectin levels at baseline and decreasing adiponectin levels during follow-up are both associated with an increased risk of MetS. (C) 2016 Elsevier Masson SAS. All rights reserved.