Background: Exposure to disinfection by-products (DBPs) has been demonstrated to impair male reproductive health in animals, but human evidence is limited and inconsistent. Objective: We examined the association between exposure to drinking-water DBPs and semen quality in a Chinese population. Methods: We recruited 2,009 men seeking semen analysis from the Reproductive Center of Tongji Hospital in Wuhan, China, between April 2011 and May 2012. Each man provided a semen sample and a urine sample. Semen samples were analyzed for sperm concentration, sperm motility, and sperm count. As a biomarker of exposure to drinking-water DBPs, trichloroacetic acid (TCAA) was measured in the urine samples. Results: The mean (median) urinary TCAA concentration was 9.58 (7.97) mu g/L (interquartile range, 6.01-10.96 mu g/L). Compared with men with urine TCAA in the lowest quartile, increased adjusted odds ratios (ORs) were estimated for below-reference sperm concentration in men with TCAA in the second and fourth quartiles (OR = 1.79; 95% CI: 1.19, 2.69 and OR = 1.51; 95% CI: 0.98, 2.31, respectively), for below-reference sperm motility in men with TCAA in the second and third quartiles (OR = 1.46; 95% CI: 1.12, 1.90 and OR = 1.30; 95% CI: 1.00, 1.70, respectively), and for below-reference sperm count in men with TCAA in the second quartile (OR 1.62; 95% CI: 1.04, 2.55). Non-monotonic associations with TCAA quartiles were also estimated for semen parameters modeled as continuous outcomes, although significant negative associations were estimated for all quartiles above the reference level for sperm motility. Conclusion: Our findings suggest that exposure to drinking-water DBPs may contribute to decreased semen quality in humans.