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Purpose: The head and neck cancer (HNC) literature is rife with reports of differences in planned versus actual radiation doses to the parotid gland (PG) due to changes in anatomy during the course of radiation therapy. We prospectively studied and quantified changes in planned and delivered doses due to weight loss and changes in lateral neck dimensions. Methods and Materials: Sixty patients were enrolled in this prospective non-randomized observational study. The inclusion criterion was having a newly diagnosed, histologically proven squamous cell carcinoma of HNC. Weight loss (WL) and change in lateral neck dimensions (LND) were assessed weekly, and new hybrid plans were generated using interval replanning CT scans. Dose variations were monitored and extrapolated for replanning CT scans and correlated with WL and change in LND. Results: The Pearson correlation coefficients for WL and difference in Dmean of ipsilateral and contralateral PG was 0.3292 (P = .0124) and 0.4232 (P = .0010), respectively. There was significantly higher change in the Dmean of bilateral PG (Ipsilateral(I) > contralateral(C)) in patients who experienced WL of >5%. Change in LND correlated with difference in Dmean of ipsilateral PG at 0.4829 (P = .0001) and difference in D50 at 0.4146 (P < .0013). Contralateral PG correlated with difference in Dmean at 0.5952 (P < .0001). The difference in Dmean for ipsilateral PG was 1.8535 Gy for those showing reduction in LND of >1 cm compared with 0.8596 Gy (P = .0091) for those who had ≤1 cm reduction in LND. Conclusions: Either WL of >5% or reduction in LND of >1 cm can be used as an external parameter to help select patients who might benefit most from replanning and adaptive radiation therapy.