Objectives: This study evaluated the incidence of late cardiotoxicity after dose-dense and -intense adjuvant sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) for breast cancer (BC) with ≥ 4 involved ipsilateral axillary lymph nodes. Methods: Patients were enrolled from 1994 to 2001 after definitive BC surgery if ≥4 axillary nodes were involved. Planned treatment was A 90 mg/m2 q 14 days × 3, T 250 mg/m2 q 14 days × 3, C 3 g/m2q 14 days × 3 with filgrastim (G) support. Left ventricular ejection fraction (LVEF) was monitored using equilibrium radionuclide angiography (ERNA) before the initiation of chemotherapy, and after three cycles of each chemotherapeutic agent. At a median follow-up of 7 years, we obtained ERNA scans on 32 patients to evaluate the long-term cardiotoxicity of this regimen. Results: Eighty-five eligible patients enrolled on the treatment protocol. Clinical heart failure developed in one patient. Seven (8%) patients had LVEF < 50% at the end of therapy. No cardiac-related deaths occurred. Thirty-two (46%) of 69 surviving patients have consented to late cardiac imaging. At a median follow-up of 7 years, the median absolute change in LVEF from baseline was -5.5%; [range (-8%) to (+36%)], and from the end of chemotherapy was -2.0%; [range (-25%) to (+16%)]. Four patients (12%) had a LVEF < 50%; two of these four patients had an LVEF of < 50% at the end of chemotherapy. Conclusions: Late development of asymptomatic decline in cardiac function may occur after dose-dense and -intense adjuvant therapy, but is uncommon. © 2006 Springer Science+Business Media, LLC.