Throughout the world cost-efficient Naphtha streams are available in refineries. Owing to less processing, CO2 emissions emitted in the course of production of these fuels are significantly lower than with conventional fuels. In common CI/SI engines, however, the deployment of Naphtha is considerably restricted due to unfavourable fuel properties, e.g. low cetane/octane numbers. Former investigations illustrated high knocking tendency for SI applications and severe pressure rise for CI combustion. Moreover, the focus of past publications was on passenger vehicle applications. Hence, this paper centers on heavy-duty stationary engine applications. Consequently, measures to increase the technically feasible IMEP with regard to limitations in knocking behaviour and pressure rise were explored whilst maintaining efficient combustion and low emissions. Investigations were conducted on two heavy-duty single cylinder research engines equipped with cooled EGR, fully indicated setup and exhaust measurement systems complying with stationary engine emission regulations. Two different kinds of Naphtha, representative to two Naphtha streams found in a refinery, were investigated. A comparison of both combustion modes regarding limits of IMEP, mechanical strain and emissions has shown promising potential: In CI combustion mode, an adapted pilot injection strategy significantly reduced pressure rise and therefore the operation range could be extended to cover the same load range as common heavy-duty applications. Further optimisation involving EGR rate and rail pressure variations exhibited benefits regarding efficiency and emission reduction. Nevertheless an exhaust after-treatment of one emission product has to be implemented. As for SI combustion, reduction in knocking behaviour could be achieved by introduction of EGR and CNG to the combustion. Hence a major expansion of load-range could be attained, which showed significant benefits in terms of efficiency, combustion stability and emissions over both pure Naphtha and pure CNG operation.