Optimization of the Sequencing Batch Reactor (SBR) operating1 conditions for high-strength non-penicillin pharmaceutical wastewater treatment is a challenging task. Two SBR were operated under different operating conditions. Three different Hydraulic Retention Times (HRT) (12, 24 and 48 h) were tested and operated under high (6000 mg L-1) and low (4000 mg L-1) Mixed Liquor Suspended Solids (MLSS) concentration. Statistical analysis (two-way ANOVA) using SPSS software was applied on the results to evaluate the effect of HRT and MLSS concentration on the SBR performance. The hydraulic retention time of 24 h was found suitable for the SBR and increasing HRT from 12 to 24 h significantly affected the BOD5 removal; however, increasing HRT from 24 to 48 h or increasing MLSS concentration from 4000 to 6000 mg L-1 did not significantly improve the SBR performance in terms of BOD5 removal. Under the optimum operating conditions (HRT 24 h and MLSS 4000 mg L-1), the SBR achieved an efficiency of 94±1.3 in terms of BOD5 removal and 83.9±1.7 in terms of CODremoval, with complete nitrification. ©2012 Asian Network for Scientific Information.