This paper describes the optimal operating conditions of diesel and dimethyl-ether (DME) fuel in a diesel engine calculated using the genetic algorithm (GA) method. In order to determine the optimal operating conditions for reducing exhaust emissions and fuel consumption, numerous calculations were performed at various operating conditions using the KIVA-3V code. In addition, different variables of the operating conditions investigated were varied, such as the start of injection (SOI), injection pressure, injection angle, and equivalence. Furthermore, the merit functions, which represent the exhaust emissions and fuel efficiency, were determined for the analysis of the optimization conditions. It is shown that the value of the merit function was attained at each successive generation number until its maximum value was reached. In addition, the optimal cases of diesel and DME fuels that elicited lower NO emissions and improved fuel consumption in comparison to baseline cases with the same fuels were found using the optimization methodology. The combustion phasing of the optimal case was shown to be retarded compared to that of the baseline case. On the other hand, the equivalence ratio of the optimal case with the use of DME fuel can be reduced compared to that of diesel fuel due to the soot-free generated during DME combustion. (C) 2016 Elsevier Ltd. All rights reserved.