Composting of manure may lead to the degradation of veterinary antimicrobials, but it is largely unknown if the presence of antimicrobials affects the composting process. Open-air windrow composting of manure from beef cattle (Bos taurus) administered chlortetracycline, sulfamethazine, and tylosin was investigated in a 2-yr study. At windrow construction, chlortetracycline had extensively isomerized to iso-chlortetracycline. Sulfamethazine, tylosin, and iso-chlortetracycline dissipated by first-order kinetics, whereas the dissipation of enol/keto-chlortetracycline was better described by exponential equations. At the end of the composting period, proportions of antimicrobials remaining were as follows: iso-chlortetracycline (< 1%), chlortetracycline (1 to 4.5%), tylosin (6.3%), and sulfamethazine (6.8% [2005], 41% [2006]). Times for 50% dissipation (DT50) decreased in the order: tylosin (20.3 to 43.5 d) > iso-chlortetracycline (13.5 to 26.5 d) > enol/keto-chlortetracycline (5.5 to 9.8 d). The DT50 values for sulfamethazine varied from 26.8 d in 2005 to 237 d in 2006. Treatments with chlortetracycline showed significantly reduced temperature rises (10.1 to 11.0 degrees C) between Days 21 to 28 in 2006 compared with rises of 26.6 to 31.0 degrees C for control and tylosin treatments, suggesting an inhibition of microbial activity. During composting in 2005, manure from cattle administered chlortetracycline at 44 mg kg(-1) of feed lost significantly less dry matter, carbon, and nitrogen than manure from cattle fed 11 mg chlortetracycline kg(-1) of feed, implying that the higher level of chlortetracycline inhibited microbial decomposition of organic matter. The study shows that while composting leads to dissipation of antimicrobials, the microbially driven composting process may be inhibited by their presence.