The analysis of energy use is important in emerging economies and especially in the manufacturing industries, as energy is a key factor of sustainable development. This research analyses and evaluates the features of regional energy use and efficiency across Colombian departments in the manufacturing industries for the period between 2005 and 2013 by applying two Malmquist data envelopment analysis models. The results indicate significant difference in energy use and efficiency across Colombian departments in the manufacturing industries. The results of the Malmquist indexes determine that various manufacturing industries across Colombian departments have a high potential to increase energy efficiency. Several manufacturing industries across Colombian departments have experienced gains in productivity, a growth in efficiency, an improvement in the relationship between inputs and outputs and scale production and advances in innovation through new technologies. This technique allows to make comparisons and improves energy policies to increase energy efficiency and decrease CO2 emissions. The application of panel data models indicate that increases in energy prices, exports and productivity lead to better energy use, while a higher presence of energy intensive sectors and small and medium enterprises across Colombian departments reduce energy efficiency. The methods selected in this research generated consistent, robust and reliable estimates related to energy use and CO2 emissions for regional studies. The findings of this study indicate that diverse energy policies should implement in the industrial sector across Colombian departments and that they should contribute to improvements in energy use, especially in small and medium companies and energy intensive sectors.