New treatment approaches that include the use of aromatase inhibitors in adjuvant breast cancer management are associated with higher efficacy and increased drug costs. Our aim was to calculate the difference in total costs of care associated with two therapeutic options, anastrozole and tamoxifen, from the perspective of a healthcare provider. The cost of care and a decision tree analysis were used in this assessment. The efficacy of both drugs in terms of relapse rate was obtained from an ATAC (Arimidex, Tamoxifen Alone or in Combination) trial after the median observational time of 68 months. The total sum of all direct healthcare costs over a 60-month period was 14,438 and 8,009 Euros per person in the anastrozole and tamoxifen arm, respectively. Despite higher total costs of care associated with anastrozole, the drug cost ratio of anastrozole/tamoxifen=8.1/1 converted to a ratio of only 1.75/1 in favor of tamoxifen when costs of recurrence and adverse events were included. The total costs of care, including disease recurrences and adverse event management obtained in our analysis were similar to total costs of care values for other surveys, which lead us to believe that anastrozole is also a cost-effective alternative to tamoxifen in Slovenia.