RATIONALE: Acetaminophen has been hypothesized to increase the risk of asthma and allergic disease, and geohelminth infection to reduce the risk, but evidence from longitudinal cohort studies is lacking. OBJECTIVES: To investigate the independent effects of these exposures on the incidence of wheeze and eczema in a birth cohort. METHODS: In 2005-2006 a population-based cohort of 1,065 pregnant women from Butajira, Ethiopia, was established, to whom 1,006 live singleton babies were born. At ages 1 and 3, questionnaire data were collected on wheeze, eczema, child's use of acetaminophen, and various potential confounders, along with a stool sample for geohelminth analysis. Those without wheeze (n = 756) or eczema (n = 780) at age 1 were analyzed to determine the independent effects of geohelminth infection and acetaminophen use in the first year of life on the incidence of wheeze and eczema by age 3. MEASUREMENTS AND MAIN RESULTS: Wheeze and eczema incidence between the ages of 1 and 3 were reported in 7.7% (58 of 756) and 7.3% (57 of 780) of children, respectively. Acetaminophen use was significantly associated with a dose-dependent increased risk of incident wheeze (adjusted odds ratio = 1.88 and 95% confidence interval 1.03-3.44 for one to three tablets and 7.25 and 2.02-25.95 for ≥ 4 tablets in the past month at age 1 vs. never), but not eczema. Geohelminth infection was insufficiently prevalent (<4%) to compute estimates of effect. CONCLUSIONS: These findings suggest frequent acetaminophen use early in life increases the risk of new-onset wheeze, whereas the role of geohelminth infection on allergic disease incidence remains to be seen as the cohort matures.