Our objective was to validate the International Harmonization Project (IHP) positron emission tomography (PET) response criteria and correlate with the Deauville criteria and diagnostic computed tomography-based (dCT) lesion size changes. All patients were recruited prospectively to the Cancer and Leukemia Group B (CALGB) 50203 trial for the treatment of stage I-II, non-bulky Hodgkin lymphoma (HL). [(18)F]Fluorodeoxyglucose (FDG) PET and dCT were performed at baseline and after two doxorubicin, vinblastine and gemcitabine (AVG) cycles (PET-2, dCT-2) in 88 patients. IHP and Deauville criteria and percent decrease in the sum of the products of the perpendicular diameters (%SPPD) after two cycles were correlated with progression-free survival (PFS). After a median follow-up of 3.3 years, 23.9% of patients relapsed/progressed (3-year PFS 77%). By IHP, the 2-year PFS was 88% and 54% for PET-2 negative and positive groups, respectively (p = 0.0009). Similar results were obtained for Deauville criteria. In a univariate analysis, PET-2 predicted PFS better than %SPPD, and in a combinatorial analysis, in the PET-2 positive group, a negative dCT-2 increased PFS by 27-35%. However, some confidence intervals were large due to small sample sizes. In conclusion, IHP and Deauville criteria-based interpretation of PET-2 was strongly associated with 2-year PFS. The combined analysis of PET-2 with dCT-2 suggested a better predictive value for PFS compared to either test alone. Further studies are under way to confirm these findings.