Background: CCRT using 3 weekly cisplatin (DDP) 100mg/m² is considered standard nonsurgical option for LAHNSCC. Many prefer DDP 40 mg/m² weekly assuming this to be non inferior, with better radio sensitization, and less toxic but without robust supporting evidence. We designed this non inferiority trial to compare 3 weekly DDP to weekly DDP. Methods: Multicentric non inferiority RCT to compare DDP 100 mg/m² (Control as C) 3 weekly x 3 times to 40 mg/m² (Test as T) weekly DDP x7 times with concurrent RT as definitive therapy in non nasopharyngeal LAHNSCC. Primary objective was 2 years loco regional control (LRC) rates. Secondary endpoints included OS, PFS, toxicity, compliance, others. Assuming LRC of 60%, power of 80%, alpha error of 5%, and non inferiority margin of 10% 143 patients in each arm were required (including 10% non evaluable etc). Results: Between April 2018 and January 2021, 278 were randomised. Median age was 56 years (range 19-70), 89.6% were males. Primary sites were, oropharynx (59.6%), larynx (17.5%), hypopharynx, and oral cavity (11.6%) each. TNM stage was, stage III (29.1%), stage IVA (50.5%), and IVB (20.4%). 13% of oropharyngeal who were tested for p16 were found positive. ECOG PS was 0-1 in 78.9%. 135 in each arm were eligible for treatment and 132 received some form of treatment. Baseline characteristics (Chi square/Fisher’s exact test) were well balanced except higher number of patients with LVEF <50% in T arm (p=0.035). 87.2% of patients in C arm, and 81.6% in T arm received ≥ 60 Grays (p=.94), 78.6% in C and 81.6% patients in T arm received ≥ 200 mg/m2 of DDP (p=.31). There were more treatment delays in treatment in C arm (p=NS). Treatments interruptions (p=0.035), hospitalizations (p=0.004), use of additional IV fluids (p= <.001), mucositis (p=.029), myelosuppression (P=.021), renal toxicity (p=<.001), vomiting ((p=.002), hyponatremia (p=.004) were all significantly more in C arm. There were 10 toxic deaths in C arm and 7 in T arm. 81.6% in C arm and 85.4% patients in T arm achieved CR+PR (p=.055). LRC rates at 2 years were 57.69% in C arm and 61.53% in T arm, with an absolute difference of 3.84% and (one sided 95% CI= -6.15, 13.80) which is within the pre defined non inferiority margin of -10%. Cumulative 2 year LRC rates were 52.6% in T and 47.4% in C (log-rank p=0.426; HR 0.86 [95%CI: 0.60-1.23]) by parametric survival estimates with an absolute difference of 5.2% (95%CI= -7.7, 18.2) again within pre defined margin. There was no significant difference in median time to loco-regional failure (C=21.23 months and T= NR; p=.45), OS (C=30.50 months and T= 25.46; p=.59) and PFS (C=20.60 months and T= 20.66; p=.46). Conclusions: This academic trial confirms that CCRT with weekly DDP is non inferior to 3 weekly DDP, is better tolerated with less interruptions, hospitalizations, and toxicity and should now be considered as one of the standards. Clinical trial information: CTRI/2018/03/012422.