Background: Records from the cancer registry system of Iran indicate that colorectal cancer is the third most common cancer in Iranian men and fourth most common among Iranian women. In this study we have investigated the environmental factors associated with colorectal cancer in Isfahan, Iran.Methods: In this case-control study, we randomly selected 187 patients with colorectal cancer who had positive results by colonoscopy and pathology (case group) and 250 persons who had negative colonoscopy results (control group) from the Colonoscopy Unit of Al Zahra Hospital and Colorectal Cancer Center of Seyed Al Shohada Hospital from 2014 to mid-2015. This study aimed to find the risk factors for sporadic colorectal cancer; therefore, we excluded patients with positive family history. Participants completed a self-administered questionnaire that asked about sex, age, body mass index, smoking status, job-related physical activity, and nonsteroidal antiinflammatory drug consumption.Results: This study enrolled 187 colorectal cancer patients (98 males and 89 females) and 250 individuals without colorectal cancer (107 males and 143 females). Multiple analysis demonstrated a significant association of age (odds ratio: 1.04; 95% confidence interval: 1.02, 1.06) and body mass index (odds ratio: 1.09; 95% confidence interval: 1.03, 1.15) with colorectal cancer risk. Men had an almost two-fold risk compared with women (odds ratio: 1.85; 95% confidence interval: 1.14, 2.99). Subjects who did not use nonsteroidal anti-inflammatory drugs had an almost three-fold risk compared with nonsteroidal anti-inflammatory drug consumers (odds ratio: 0.34; 95% confidence interval: 0.19, 0.62). Analysis for job-related physical activity, also indicated an association between the no/low active group with colorectal cancer (odds ratio no activity: 36.09; 95% confidence interval: 10.94, 119 and odds ratio low activity: 2.96; 95% confidence interval: 1.43, 6.13).Conclusion: Knowledge of the risk factors involved in colorectal cancer incidence makes it possible to identify people at risk and begin risk reduction strategies as well as screening programs.