Anaerobic digestion was carried out in this study using the shoot of Tithonia diversifolia using a consortium of microorganisms. Combinations of mechanical and thermo-alkaline (Sodium hydroxide and Potassium hydroxide) pretreatments were applied to two samples (X and Y) of the mixture while the third sample (Z) had no thermo-alkaline treatment. Prior to pretreatment, the Central Composite Design was used for optimizing the pretreatment temperature and time. The physicochemical characteristics of T. diversifolia shoot were carried out using standard methods. Modeling of the generated biogas data was done using the Response Surface Methodology. The optimal conditions for this process were statistically predicted as Temperature (S-1) of 30.00 degrees C, pH (S-2) of 7.5, Retention time (S-3) of 30 day, Total solids (S-4) of 12.00 g/kg and Volatile solids (S-5) of 4.00 g/kg. The most desired predicted biogas yields under these conditions were 2249.24, 1519.15 and 1043.50 . 10(-3)m(3)/kg TSfed with the desirability values of 1.000 (100%) in all cases. Analyses revealed the average gas composition to be within the range of 65 +/- 1% methane and 26 +/- 2% carbon dioxide for digestion 'X'; 59 +/- 1.5% Methane and 22.5 +/- 2%% Carbon dioxide for digestion 'Y' while it was 53 +/- 2% Methane and 20.5 +/- 2% Carbon dioxide for digestions 'Z'. The roots mean squared error, coefficient of determination, and the predicted value were used to determine the fitness of the model. All the obtained values show that the model had a high predictive ability for the study. The energy assessment showed positive energy balances from the thermoalkaline pretreated experiment and this can be increased via the use of higher substrate loading in order to increase the economic feasibility of the applied pretreatment. In locations where T. diversifolia is abundant, its usage for biofuel could be a lead to solving the prevailing energy crisis. (C) 2017 Elsevier Ltd. All rights reserved.