OBJECTIVES: Breast-cancer is the most frequent malignancy amongst women in Europe and therefore represents a major public-health problem. The purpose of this analysis was to estimate the cost-effectiveness of AT (doxorubicin, docetaxel) compared with AC (doxorubicin, cyclophosphamide), CMF (cyclophosphamide, methotrexat, 5-fluoruracil) and FEC (5-fluoruracil, epirubicin, cyclophosphamide) administered as adjuvant therapy to women with node-positive breast-cancer across four European countries (Spain, Italy, Germany and Belgium). METHODS: We developed a multi-country Markov-model to simulate the long-term consequences from initiation of adjuvant chemotherapy over 10 years. The model simulates the incidence of complications during chemotherapy (febrile neutropenia, chemotherapy-induced nausea/vomiting, dose-reduction, dose-delay, grade 3/4 adverse events) and long-term consequences like local or distant-relapse, acute myelogenous leukemia (AML), chronic heart failure and death. Monte-Carlo-simulation accounted for uncertainty. The model includes twelve health-states. Probabilities were derived from clinical and epidemiological studies; direct costs (2011) from published sources from the payer’s perspective. QALYs, life-years (LYs) and costs were discounted at 5% p.a.  RESULTS: Over a 10-year timeframe, costs associated with AC are 13,266€, 14,826€, 15,699€ and 16,558€ for Spain, Italy, Germany and Belgium, respectively. AC is associated with 5.85 QALYs (6.49 LYs). Costs for AT amount to 15,362€ (Spain), 19,004€ (Italy), 19,768€ (Germany) and 20,625€ (Belgium) and AT delivers a similar benefit to AC: 5.85 QALYs (6.50 LYs). The resulting opportunities for cost-savings with AC vs. AT are between 2,096€ (Spain) and 4,178€ (Italy). Costs associated with CMF are 14,145€ (Spain), 15,609€ (Italy), 16,411€ (Germany) and 16,924€ (Belgium); 5.8 QALYs (6.4 LYs) are gained. AC dominates CMF. FEC associated total costs are 15,138€ (Spain), 15,652€ (Italy), 17,431€ (Germany) and 17,492€ (Belgium). QALYs are 6.03 (6.81 LYs). FEC dominates AT in all four countries.  CONCLUSIONS: Cyclophosphamide-based regimens (FEC, AC and CMF) demonstrate a better performance from cost-effectiveness perspective vs. AT in the four European countries.