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PFOA (perfluoroctanoic acid) is a perfluoroalkyl substance (PFAS). Although use in the US has been phased out, PFOA persists indefinitely in the environment, and is present in the serum of virtually all people in industrialized countries. Approximately 6 million Americans drink water comtaminated with PFOA above EPA-recommended levels. In a previous cohort study (n = 32,000), we found a strong positive exposure-response relation between PFOA serum levels and subsequent ulcerative colitis (UC) in a high-exposed population from the mid-Ohio valley, but no association with Crohn's disease. In the present study we aimed to determine if UC cases had higher levels of PFOA than did controls or Crohn's disease patients.We measured PFOA and three other PFAS in the serum of 114 UC patients, 60 Crohn's disease patients, and 75 controls, within a year of diagnosis. We conducted regression analyses to assess the association of the PFAS with diagnosis.The mean age of subjects was 17 years. The mean year of diagnosis was 2007. Mean levels of PFAS were similar to US levels. Mean log PFOA level in UC patients was 38% higher (p = 0.01) than the combined group of Crohn's disease and controls. In contrast, the three other PFASs were significantly higher in controls and Crohn's patients than UC patients. The odds ratio for UC per one unit of log PFOA was 1.60 (95% CI 1.14–2.24), but the trend by quintiles was not monotonic (1, 0.84, 40.98, 33.36, 2.86).We found higher serum PFOA in UC cases compared to Crohn's disease patients or controls, in contrast to other PFAS. Our research is limited by not knowing if the elevated PFOA preceded UC in this population.PFOA was strongly associated with ulcerative colitis (UC) in a prior cohort study.We measured PFOA in UC patients and controls within a year of diagnosis.Log PFOA was significantly higher (38%) in cases compared to controls.Other perfluoroalkyl substances (PFAS) were lower in controls than cases.Our study is limited by being cross-sectional by PFOA measured after diagnosis.