Background: Surgical resection is considered to be of purely diagnostic value in aggressive lymphoma. Evidence for an impact on outcome is scant and restricted to retrospective observations. Methods: In the “Positron Emission Tomography-guided Therapy of Aggressive non-Hodgkin Lymphomas” (PETAL) trial, patients with a negative baseline positron emission tomography (PET) scan were documented in a prospective observational substudy. Baseline PET-negative patients with the absence of lymph node enlargement on computed tomography and a negative bone marrow biopsy were considered to have undergone complete lymphoma resection. Results: Eighty-two of 1,041 patients (7.9%) had a negative baseline PET scan, and 67 were included in this analysis. All were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), plus rituximab for CD20-positive lymphomas. Among 52 patients with diffuse large B-cell lymphoma (DLBCL), 48 had completely resected disease. Their outcome tended to be better than that of 115 baseline PET-positive stage I DLBCL patients treated in the main part of the PETAL trial (2-year progression-free survival 92.7% [95% confidence interval 84.7-100] versus 88.4% [82.5-94.3], P =.056; 2-year overall survival 92.7% [84.7-100] versus 93.7% [89.2-98.2], P =.176), but this was restricted to patients below the age of 60 years (2-year progression-free survival 100% versus 92.2% [84.8-99.6], P =.031; 2-year overall survival 100% versus 95.9% [90.2-100], P =.075). In peripheral T-cell lymphoma, eight of 11 patients had completely resected disease. In contrast to DLBCL, complete resection was not associated with improved outcome compared to the control. Conclusion: Young patients with early stage DLBCL may benefit from complete lymphoma resection prior to immunochemotherapy.