: This study aimed to determine whether interim PET/CT (iPET) scans could identify follicular lymphoma (FL) patients at high risk of relapse following first-line therapy. : A total of 117 FL patients who underwent iPET scans were included, with responses interpreted using the Deauville score (DS). Progression-free survival (PFS) was evaluated over a median follow-up of 34 months. : Overall, 34% of patients were classified as iPET (+), with significantly worse estimated 5-year PFS compared to iPET (-) patients (34% vs. 76%, hazard ratio 4.3, < 0.001). Multivariate analysis confirmed iPET (+) as an independent predictor of PFS. : Interim PET results are significant predictors of PFS in FL first-line therapy and could inform response-adapted treatment strategies.