Transformation of organic waste to energy is a complex process which involves hundreds of possible intermediate compounds and reactions. Simulation process can provide suitable assessment of a bioconversion system before its actual fabrication and commercialization. In addition, process simulation is a suitable tool for optimization of technical factors (e.g., bioreactor configuration and conversion units design) and economical factors (e.g., throughput, production cost, revenue and gross margin). In this study, biodegradation process of a small-scale anaerobic bioreactor was simulated using SuperPro Designer®. Process simulation flow sheet, materials registration and process reactions were conducted during model setup. Next, model validation was carried out by comparison between the outputs and actual data achieved during experimental phase. Results show the appreciable agreement between predicted and actual data due to appropriate process definition during simulation. Two different bioreactor configurations were investigated and efficiency and performance of each pattern was tested based on biogas production rate, methane content in biogas and biochemical and chemical oxygen demands (BOD and COD) removal efficiencies. Finally, economical analysis was performed in the model which indicates, biogas production from organic waste in a single small-scale bioreactor is a promising method for renewable energy generation. © 2012 Asian Network for Scientific Information.