Oxytetracycline degradation inside UV/H 2O 2 system was carried out through mediation of hydroxyl radical attack which oxidizes recalcitrant, toxic and non-biodegradable compounds to various by-products. The Box-Behnken design of experiment was applied to find the optimum condition of OTC degradation. Three levels fractional design which consist of a full 2 2 factorial with three centre points resulted incomplete block design were resulted from the chosen design. Temperature at 30-50°C, pH range 3-11 and oxidant/pollutant ratio 0.5:1-1.5:1 were chosen as the experimental factors. Total organic carbon was measured for monitoring degradation efficiency. Percentage of total organic carbon removal was chosen as the response. Based on Pareto chart, the quadratic effect of pH was the most significant factor that minimizes percentage of total organic carbon removal. As suggested by the model, the maximum total organic carbon removal could be obtained at 30°C, pH 6.30 and 1.5 mole equivalent of oxidant/pollutant ratio. At its optimum condition, about 95.35 and percentage total organic carbon removal was achieved. At the optimum condition, the ratio of BOD 5/COD value was 1.19, which implied the biodegradability of the degradation product of oxytetracycline. © 2012 Asian Network for Scientific Information.