AIMS: The aim of this study was to determine if head and neck squamous cell carcinoma (HNSCC) patients treated with cisplatin chemoradiotherapy and short hydration (SH) experience less dose-limiting toxicity (DLT) and receive more cisplatin than those with medium hydration (MH) or long hydration (LH). METHODS: Baseline characteristics, cumulative cisplatin dose and toxicities were collected. Differences between LH, MH and SH were tested, with separate analyses for triweekly 100 mg/m RESULTS: A total of 389 patients were included. DLT occurrence was comparable between hydration groups (P = .060), but DLT type differed (P = .007). Nephrotoxicity was common with LH and MH (n = 11, 61% and n = 26, 45%, respectively), and ototoxicity with SH (n = 35, 36%). DLT occurrence in triweekly patients differed between LH and MH (n = 18, 64% vs n = 25, 32%, P = .004), but not between MH and SH (P = .171) or LH and SH (P = .055) patients. Cisplatin dose differed between LH and MH (median 200 vs 300, P = .008) as well as between LH and SH (median 200 vs 300, P = .024) but not between MH and SH (P = .429) patients. Hydration had no effect on dose (F = 2.09, P = .125). CONCLUSIONS: DLT cause differed between hydration groups, with less nephrotoxicity but more ototoxicity in HNSCC patients with SH. Triweekly cisplatin LH patients had more DLT and lower cumulative dose compared to MH and SH, but no hydration effect in general on dose was found.