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Abstract: Quantification of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) can be time-consuming. We evaluated the performance of an automatic multi-foci segmentation method of quantification (MFS) in patients with different stages of Hodgkin's Lymphoma, using the multiple VOI method (MV) as reference. Methods: This prospective bicentric study included 50 patients with Hodgkin's Lymphoma who underwent staging 18F-FGD PET/CT. The exams were centrally reviewed and processed with commercial MFS software in order to obtain MTV and TLG utilizing two fixed relative thresholds (40% and 20% of the maximum standardized uptake value) of each lesion. All PET/CTs were processed using the MV and MFS methods. Inter-class correlation coefficient and Bland & Altman plots were used for statistical analysis. Repeated calculations of MTV and TLG values by two observers with different degrees of PET/CT imaging experience were used to access interobserver agreement of the MFS method. Results: The mean and standard deviation values obtained for the MTV with MV and MFS were respectively 736mL ± 856mL and 660mL ± 699mL for the 20% threshold, and 313mL ± 359mL and 372mL ± 434mL for the 40% threshold. The time spent calculating the MTV was much shorter with the MFS than with the MV method (median time: 11.6 min. [1-30 min] and 64.4min. [1-240 min], respectively), especially in patients with advanced disease. Time spent was similar in patients with localized disease. There were no statistical differences between the MFS values obtained by the two different observers. Conclusion: MTV and TLG calculations using MFS are reproducible, generate similar results to those obtained with MV and are much less timing consuming. Main differences between the two methods were related to difficulties in avoiding overlay of VOIs in the MV technique. MV and MFS perform equally well in in patients with small number of lesions