The standard first-line treatment in recurrent/metastatic head and neck squamous cell carcinoma combines Cisplatin, 5 Fluorouracil and Cetuximab, but many patients aren’t eligible. We retrospectively evaluated the efficacy and the tolerability of Carboplatin and Paclitaxel in this indication, mostly in patients unfit to Cisplatin.Paclitaxel (80mg/m2) was administered at day 1, 8 and 15 and Carboplatin area under the curve 5 at day 1, repeated every 28 days, for 6 cycles. Carboplatin could be administered at area under the curve 2 at day 1, 8 and 15.117 patients received this association at our institution, 94 of those were ineligible to cisplatin due to severe comorbidities, age >70years or Performance status >1.The overall response rate was 40%. The median progression free survival for patients ineligible to Cisplatin was 4.4 months [95% CI; 3.4; 5.0] and the median overall survival was 8 months [95% CI; 5.4–10.7].The most frequent toxicities were hematologic, with 94 grade ≥ 3, mostly in patients who received monthly Carboplatin.Our study shows Carboplatin and Paclitaxel in first-line in recurrent/metastatic head and neck squamous cell carcinoma appear efficient for patients ineligible to Cisplatin and safe when both drugs are weekly administered.