The aims were to assess the prevalence of resistances to antiretroviral drugs in HIV patients in the province of Cuenca and to determine the most frequently detected primary resistances. A total of 79 samples collected from April 2000 to July 2004 were analyzed. Resistance was detected using the genotypic technique VERSANTTM HIV1 (LiPA). Mutations more frequently found were M184V in the reverse transcriptase gene and V82A in the protease gene. The prevalence of primary resistances was 39.4%. Mutations more frequently detected were similar to those reported by other authors. The rate of primary resistance was higher than those found by other authors in Spain.