Evidence suggests a link between adiponectin, an adipocytokine, and liver tumorigenesis. Different multimercomplexes of adiponectin, with low-molecular weight (LMW), middle-molecular weight (MMW) and highmolecularweight (HMW), may have different roles. Therefore the present study was performed with the aim ofassessing associations between these multimers and liver cancer development. A nested case-control study (59liver cancer cases [mean age=63.5 years] and 334 controls [62.7 years]) was conducted as a part of the JapanCollaborative Cohort (JACC) Study recruiting healthy participants, aged 40-79 years, for the follow-up periodfrom 1988-1990 to 1999. The end point was liver cancer occurrence/death. Serum levels of HMW, MMW andLMW adiponectin were determined at baseline using an ELISA assay. Multivariate-adjusted logistic regressionanalyses comparing the tertile levels of adiponectin multimers showed that the groups stratified with the highestpercentage of LMW tended to have lower odds ratios (ORs) than the lowest group (OR adjusted for sex, ageand area=0.54 [95%CI: 0.26-1.11] and adjusted for sex, age, area, body mass index, smoking, alcohol, coffeeconsumption, diabetes history and HCV-antibody positivity =0.50 [95%CI: 0.22-1.15]), albeit without statisticalsignificance (set at p<0.05). Higher percentages of circulating LMW adiponectin may lead to a reduction of livercancer risk and relationships with multimer composition may merit further study.