The purpose of this study was to quantify the potential dosimetric impact of delineation variability (DV) in head and neck radiation therapy (RT) when inherent patient setup variability (SV) is also considered. The impact of DV was assessed by generating plans with multiple structure sets, cross-evaluating them, including SV, across sets, and determining P : the probability of achieving organ-specific plan quality metrics (PQM). DV was incorporated by: (1) using multiple organ at risk (OAR) structure sets delineated by independent manual observers; and (2) randomly perturbing manually generated OARs to generate alternatives with varying levels of uncertainty (low, medium, and high DV). For each structure set, independent VMAT plans were auto-generated to meet clinical PQMs. Each plan was cross-evaluated using OARs from multiple structure sets with simulated SV including per-fraction random (σ ) and per-treatment-course systematic (Σ) setup errors. The dosimetric impact of DV was assessed by examining P with and without SV/DV. Clinically significant differences were defined by those that exceeded differences caused by a  +2% output variation. Without including SV, simulated DV at the medium level reduced P by an average of 5.5% for all OARs with D PQMs. This reduction decreased to 2.8% for SV  =  2 mm and 2.4% for SV  =  4 mm (the average P reduction due to 2% output errors was 2.7%). For OARs with D PQMs, the average P reduction was 0.9% for SV  =  0 and  ⩽0.1% for SV  ⩾  2 mm. The effect of DV was larger for OARs that directly abutted a target volume than for those that did not. These trends were also observed with real DV from multi-observer delineations. The dosimetric impact of DV appeared to decrease when random and systematic SV was considered. Sensitivity to DV was affected by OAR objective type (i.e. D versus D objectives) as well as distance from the target volume.