OBJECTIVES: The ABCSG-12 trial demonstrated that adding zoledronic acid 4 mg IV q 6 months (ZOL) to endocrine therapy with goserelin 3.6 mg sc q 28 days plus tamoxifen 20 mg oral qd or anastrozole 1mg oral qd (ET) in premenopausal women with hormone receptor positive (HR+) early breast cancer (EBC) improves disease free survival versus ET alone. The objective of this study was to estimate the cost-effectiveness of ZOL in this setting from the Greek health care system perspective. METHODS: A Markov model was used to project lifetime outcomes and costs of breast cancer care for premenopausal women with HR+ EBC receiving 3 yrs of ET or 3 yrs of ET plus ZOL. Cost-effectiveness was measured as the incremental cost per quality adjusted life year (QALY) gained. Probabilities of breast cancer recurrence were based on ABCSG-12. Probabilities and costs were from the published literature. Results were generated under 2 scenarios: 1) benefits of ZOL persist to the 7 yr maximum follow-up in ABCSG-12 (trial benefits) and 2) benefits persist until recurrence or death (lifetime benefits). RESULTS: Expected costs of 3 yrs of ZOL (medication and administration) were €1802. Under the trial benefits scenario, costs of breast cancer recurrence were reduced by €58; ZOL was therefore projected to increase total costs by €1764.  Under the lifetime benefits scenario, costs of breast cancer recurrence were reduced by €1548; total expected lifetime costs were therefore increased by €273. QALYs gained with ZOL were 0.43 years under the trial benefits scenario and 1.39 years under the lifetime benefits scenario. Cost per QALY gained was €4102 and €196 under the two scenarios, respectively. CONCLUSIONS: Adding ZOL to ET in premenopausal women with HR+ EBC is highly cost-effective from the Greek healthcare system perspective even under conservative assumptions regarding the duration of ZOL benefits.