This study analyzed direct and indirect relationships in water consumption by Macedonian economic sectors using virtual water in an input–output framework. Macedonia was found to be characterized by intensive water consumption, with some sectors having a significant virtual water content in their products. Virtual water multipliers were used to analyze the trade balance and determine whether national commercial trade strategies are in line with Heckscher–Ohlin (HO) theory. It was found that Macedonia trade strategies in terms of virtual water were generally in line with HO theory. However, as a consequence of significant exports and high virtual water content in vegetables, fruit, grapes and sheep and goat products within the agriculture sector and in food and basic metal products in the manufacturing sector, the region was a net exporter of virtual water, losing about 124 million m3 of water at 2005 level or 18% of total water consumption. Reducing exports of the most water-intensive products with significant net positive exports would result in substantial water savings of 42% of total water consumption. The results presented here can help policy makers in promoting production specializations that are more environmentally sustainable or in redesigning existing water pricing policies at national level to encourage rational use of water.