Delay in radiation therapy (RT) as part of multimodality therapy in Hodgkin (HL) and non-Hodgkin lymphoma (NHL) is associated with worse pain scores. In a heterogeneous cohort of lymphoma patients, we hypothesize that interdigitating RT before fewer (versus more) lines of chemotherapy (C) will be associated with lower opiate analgesic requirement. From 2009-2019, patients with HL or NHL received palliative (36.5%) or definitive (63.3%) RT at a single institution. An IRB approved database with baseline treatment/disease characteristics, including oral morphine equivalent (OME) requirement, was reviewed. OME was recorded for a) 3-month period prior to RT, b) the month during RT, and c) 3 months after RT. Post-RT change in OME was calculated as the difference in "b" and "c" such that greater or less OME use post-RT was defined as positive or negative value respectively. We performed one-tailed t-test analyses to determine differences in OME during RT between different cohorts. Correlations between baseline characteristics and OME were performed using Spearman correlations, controlling for lymphoma subtype, stage, tumor volume, relapsed/refractory disease, duration of radiation and bulky disease. Of 180 patients, 57.8% had NHL, 40.6% were stage IV and 29.4% had bulky disease. At median of 19 days [6-80] from diagnosis, 74% of patients received C with a median of 2 lines [1-4] before RT. The median interval from diagnosis to RT was 11 months [4-36]. Pearson correlation showed a negative association between time from diagnosis to RT and postRT OME in the definitive cohort (R2 = 0.42, F = 4.54, p = 0.002) such that the longer the time to RT, the larger the decrease in OME postRT as compared to during RT. T-test showed higher mean OME during RT for those receiving > 2 lines of C preRT (148.3mg) as compared to those receiving ≤ 2 lines before RT (51.5mg, p = 0.02). In patients receiving definitive RT, the difference remained significant: those receiving >2 lines of C had higher OME during RT as compared to those receiving ≤ 2 lines (207.5mg versus 48.3mg, p = 0.02). The difference in mean OME for patients receiving >2 C lines versus ≤ 2 lines was not significantly different in the palliative cohort (75.6 vs 60.6, p = 0.33). OME use during RT was also found to be higher in patients with bulky disease as compared to non-bulky disease (175.7 versus 52.0, p = 0.04). In our single-center experience, patients who received >2 lines of C prior to RT were found to have a significantly higher mean OME requirement during RT. In patients receiving definitive RT, longer time to receipt of RT was found to be associated with a larger decrease in OME post-RT, likely related to starting with a higher OME. Interdigitation of RT early on, prior to the 3rd line of chemotherapy, may help reduce pain and improve quality of life.