Our retrospective analysis compared the effectiveness of conventional antracycline-containing protocols (A+) and docetaxel/epirubicine (TE) as primary systemic chemotherapies (PSCT) for inflammatory breast cancer (IBC). Seventy IBC patients received either A + (n = 48) or TE (n = 22) as PSCT. The objective clinical response and clinical benefit rate of treated patients were 54.3% (A+: 54,2% vs. TE: 54,5%; p = 0,28) and 92.8% (A+: 91,7% vs. TE: 95,5%; p = 0,57), respectively. The clinical complete response rate (cCR) was 23.2% (A+: 27,1% vs. TE:4,5%; χ (2) = 4,79; p = 0,03) with 7.14% (A+: 10,4% vs. TE:0%; χ (2) = 2,47; p = 0,12) of pathological complete responses (pCR). The median progression free (PFS)/local progression free (LPFS)/overall survival (OS) was 2.0/5.4/4.0 years, respectively. Patients achieving cCR had a tendency for better survival parameters than patients with less than cCR. Response rates or survival data were not statistically different in the two chemotherapy (CT) treatment groups. The survival was not influenced by the number of CT cycles in either protocols. In this set of patients, the clinical efficacy of the two alternative primary systemic chemotherapies (A + and TE) is equivalent in the treatment of inflammatory breast cancer (IBC), despite of the significant difference in favour of A + noticed in CRs. Six cycles of CT could be enough for patients achieving CR, however sequential pre- and/or postoperative CT with non cross-resistant drugs should be considered for non-responders.