Due to the importance of potato cultivation in Nariño, Colombia and the high participation of fertilizer in production costs (25%), as well as the great variability of soils in the region, we evaluated three fertilizer levels for six cultivars of Solanum tuberosum subsp. andigena in four homogeneous production environments. We recorded physiology and yield of the potatoes in experimental plots in a randomized complete block design with three replications in each environment. Analysis of variance, comparison of means for yield components, and discriminant analysis of principal components were performed for all variables. For the economic analysis we used the partial budget net benefit methodology. The environments generated differential responses in the cultivars. Between fertilization levels there were significant differences, however, there was no interaction between levels and environments. The cultivars ‘ICA Única’, ‘Pastusa Suprema’, ‘Parda Bilingüe’, and ‘Roja Huila’, showed the highest yields with the application of 262, 600, and 538 kg ha-1 of N, P2O5, and K2O (level L3). ‘Diacol Capiro’ and ‘Superior’ did not show yield differences between levels. Economically, the alternative that would generate the highest return on investment was fertilization with level L2 (N 180, P2O5 400, K2O 358 kg ha-1) in ‘Diacol Capiro’, ‘Superior’, and ‘ICA Única’ cultivars. For ‘Roja Huila’ and ‘Parda Bilingüe’ the highest return was level L1 (N 150, P2O5 200, K2O 100 kg ha-1). In the case of ‘Pastusa Suprema’ the marginal rate of return was 18.5% with the L2 fertilization level.