The etiology of esophageal squamous cell carcinoma (ESCC) in the high risk area of northern Iran is only partially known. We aimed to investigate prolonged animal contact as a risk factor for ESCC in this population. From 2003 to 2007, we administered a validated questionnaire to 300 ESCC cases and 571 randomly selected controls matched for neighborhood of residence, age (± 2 years) and sex. Questions on lifelong exposure to equines, ruminants, canines and poultry, including duration and level of contact, were asked in a face-to-face interviews. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusted for potential confounders. A total of 94.7% of cases and 68.7% of controls reported lifelong history of contact with ruminants. After controlling for potential confounders, contact with ruminants was associated with an 8-fold increase (95% CI: 3.92 – 14.86) in risk of ESCC, and increments in duration of contact raised the risk estimates in a dose-dependent manner. Contact with equines and poultry did not significantly change associated odds ratio for ESCC risk and contact with ruminants. Odds ratio (95% CI) for contact with canines was 1.99 (1.35-2.93) which after exclusion of contact with ruminants was not significant (OR for contact only with canine: 3.18, 95% CI: 0.73 – 13.17). These results add to the evidence that contact with ruminants may increase the risk of ESCC. © 2014 Wiley Periodicals, Inc.