Sodium hydroxide (NaOH) as an alkaline pretreatment method to enhance the degradation kinetics of sugarcane straw (SCS) for methane production was investigated with a special focus on the benefits for designing the anaerobic digestion process. For that, SCS was previously homogenized by milling in 2 mm particle size and pretreated in NaOH solutions at various concentrations (0, 3, 6 and 12 g NaOH/100 g SCS) and the methane yields were determined in biochemical methane potential (BMP) tests. The obtained experimental data were used to simulate a large-scale semi-continuous process (100 ton SCS day(-1)) according to a first-order reaction model and the main economic indicators were calculated based on cash flows of each pretreatment condition. The BMP tests showed that by increasing the NaOH concentration the conversion of the fibrous fraction of the substrate to methane was not only accelerated (higher a value), but also increased by 11.9% (from 260 to 291 mL CH4 gVS(-1)). By using the experimental data to simulate the large-scale process these benefits were translated to a reduction of up to 58% in the size of the anaerobic reactor (and consequently in electricity consumption for stirring), while the methane yield increased up to 28%, if the liquid fraction derived from the pretreatment process is also used for methane production. Although the use.of NaOH for substrate pretreatment has considerably increased the operational expenditures (from 0.97 up to 1.97 C x 106year-1), the pretreatment method was able to increase the profitability of methane production from SCS since a sensitivity analysis by varying the prices of anaerobic reactor, methane and NaOH showed a less attractive payback, net present value and internal rate of return for the control condition (0 g NaOH/100 g SCS) in all analyzed scenarios. (C) 2016 Elsevier Ltd. All rights reserved.