We conducted a comprehensive systematic review of the literature on volumetric parameters and a meta-analysis of the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with head and neck cancer (HNC). METHODS A systematic search of MEDLINE and EMBASE was performed using the key words PET, head and neck, and volume. Inclusion criteria were (18)F-FDG PET used as an initial imaging tool; studies limited to HNC; patients who had not undergone surgery, chemotherapy, or radiotherapy before PET scans; and studies reporting survival data. Event-free survival and overall survival were considered markers of outcome. The impact of MTV or TLG on survival was measured by the effect size hazard ratio (HR). Data from each study were analyzed using Review Manager. RESULTS Thirteen studies comprising 1,180 patients were included in this study. The combined HR for adverse events was 3.06 (2.33-4.01, P < 0.00001) with MTV and 3.10 (2.27-4.24, P < 0.00001) with TLG, meaning that tumors with high volumetric parameters were associated with progression or recurrence. Regarding overall survival, the pooled HR was 3.51 (2.62-4.72, P < 0.00001) with MTV and 3.14 (2.24-4.40, P < 0.00001) with TLG. There was no evidence of significant statistical heterogeneity at an I(2) of 0%. CONCLUSIONS MTV and TLG are prognostic predictors of outcome in patients with HNC. Despite clinically heterogeneous HNC and the various methods adopted between studies, we can confirm that patients with a high MTV or TLG have a higher risk of adverse events or death.