The mortality rate from cardiovascular diseases is high in Serbia. Analysis of antihypertensive drugs utilization is the basis for assessment of cardiovascular pharmacotherapy appropriateness. The aim of this study was to analyze the trend in antihypertensive drugs utilization among outpatients in Niš region, South Serbia compared to some Nordic countries (Norvay, Sweden) and Australia as well as to analyze trends in educational and drug promotion activities directed to primary healthcare workers within the same region. Using the ATC/DDD methodology, we analyzed the utilization of antihypertensive drugs dispensed on prescription in the Nis region over the 2003–2007 period. The study was retrospective, based on data obtained from Central City Pharmacy Nis. Educational and drug promotion activities were noted from the records of Medical Faculty, University of Nis, and from the records of local branches of pharmaceutical companies active in Serbia. Wilcoxon’s test was used in order to calculate the statistical significance of difference. A significant increase of 79.8% (153.8/ 276.6 DDD/inhabitants/day) in antihypertensive drug consumption was observed in the same period. This analysis showed there were substantial increases in the use of diuretics (134.7%), ACE inhibitors (79.5%) and calcium channel blockers (116.1%), especially amlodipin (241.2%). During the observed period, annual numbers of educational activities and of pharmaceutical sales representatives employed within the region increased for almost one fourth. This analysis pointed to a significant increase in the use of antihypertensive drugs in the Nis region, which was matched with increase in educational and drug promotion activities within the region, so that in 2006–2007 total consumption was approximate to some referential countries (Norvay, Sweden).