PURPOSE: Consolidation radiation therapy (RT) is often recommended in diffuse large B-cell lymphoma. The current recommended dose of 30 Gy was established in the pre-rituximab and PET-CT era. We hypothesized that following a complete response to modern systemic therapy, as determined by PET-CT, a lower dose of RT would be equally effective. METHODS AND MATERIALS: Patients with diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma achieving a complete response by PET-CT (Deauville score 1-3) after ≥4 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone or rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin were eligible. Consolidation RT dose was 19.5-20 Gy. The primary endpoint of the original study was 5-year freedom from local recurrence. RESULTS: From 2010 to 2016, 62 patients were enrolled. The stage distribution was as follows: I-II (n = 49, 79%) and III-IV (n = 13, 21%). Bulky disease (≥7.5 cm) was present in 24 patients (39%). Most (n = 58, 94%) received rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone. Four cycles were administered to 34% of patients, whereas 66% received 5-6 cycles. A median follow-up was 9 years. Overall, 1 patient experienced local recurrence with freedom from local recurrence of 98% at both 5 and 10 years (95% CI, 88%-99%). Seven patients progressed outside of the RT field. Progression-free survival and overall survival at 10 years were 77% (95% CI, 62%-87%) and 80% (95% CI, 64%-89%), respectively. CONCLUSIONS: Long-term results of this phase 2 study, with a median follow-up of 9 years, did not demonstrate late local failures when patients received ∼20 Gy consolidation RT. A larger (n = 240) confirmatory study from the International Lymphoma Radiation Oncology Group evaluating ∼20 Gy of RT after ≥3 cycles of chemoimmunotherapy completed accrual in 2023.