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The role of allopurinol usage in colorectal cancer (CRC) has no definite conclusion. The aim of this study was to explore the correlation between allopurinol usage and CRC risk in Taiwan. Using the National Health Insurance Database, we conducted a case‐control study of cases who were ≥20 years old and had newly diagnosed CRC for the period from 2000 to 2013. The controls were matched to cases by age, sex, index year, comorbidities, and socioeconomic status using propensity scores. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were measured by the conditional logistic regression model. We examined 4372 cases and 4372 matched controls. A statistically significant correlation was noted between allopurinol usage and CRC risk (OR, 0.79; 95%CI, 0.69‐0.90). We used the cumulative‐defined daily doses (cDDDs) in a further subgroup analysis, the ORs decreased from tertile 1 (T1; low dose, <12 cDDDs), T2 (medium dose, 12 to 88.5 cDDDs), to T3 (high dose, >88.5 cDDDs). These values were 0.85 (95%CI, 0.69‐1.06), 0.77 (95%CI, 0.62‐0.95), to 0.76 (95%CI, 0.61‐0.94). The results indicated a dose‐response relationship between allopurinol usage and CRC risk (P for trend <.001). We thus inferred that patients with medium and high doses of allopurinol (≥12 cDDDs) had a statistically significantly decreased CRC risk. [ABSTRACT FROM AUTHOR]