Iso-butanol is a naturally occurring 4-carbon alcohol that can be obtained by processing organic crops like corn and sugarcane. An experimental and statistical investigation is carried out to analyze the effects of injection-pressure, timing and exhaust gas recirculation (EGR) on performance and emissions of a DI diesel engine fuelled with 40% by vol. of iso-butanol/diesel blend. Response surface methodology was used to model all measured responses like nitrogen oxides (NOx), smoke opacity, brake thermal efficiency (BTE) and brake specific fuel consumption (BSFC). Analysis of variance (ANOVA) revealed that all developed models were statistically significant. Interactive effects between injection pressure, injection timing and EGR for all blends were analyzed using response surface plots that were plotted using developed regression models. Optimization was performed using desirability approach of the RSM with an objective to minimize NOx and smoke emissions simultaneously with maximum BTE and minimum BSFC. Iso-butanol/diesel blend injected at 240bar pressure, 23 degrees CA bTDC under 30% EGR was predicted to be optimum for this particular engine. The predicted combination was validated by confirmatory tests and the error in prediction was found to be within 4%. (C) 2017 Elsevier Ltd. All rights reserved.