Background: The Follicular Lymphoma International Prognostic Index (FLIPI) allows physicians to stratify patients into groups with distinct prognoses, however its ability to predict the treatment efficacy has not been fully investigated. The aim of this study was to validate on this respect the FLIPI system in an independent cohort and compare it with the International Prognostic Index (IPI) used for aggressive lymphomas. Methods: Records from patients referred to our unit with a diagnosis of follicular lymphoma (FL) were retrospectively reviewed. Data required for FLIPI and IPI scores were collected along with data regarding first-line chemotherapy and time to treatment failure (TTF) and overall survival (OS). Results: Of 162 patients screened, 130 were assessable for both (FLIPI and IPI) scores. OS for low-risk (LR) patients identified either with IPI or FLIPI was significantly longer compared to intermediate-risk (IR) and high-risk (HR) groups, with FLIPI allowing a more even patient distribution among the risk groups. For patients receiving first-line chemotherapy within 6 months of diagnosis, a low FLIPI score was associated with a longer TTF (3-year TTF rates: 68.0, 33.7 and 31.0% for FLIPI-defined LR, IR and HR patients, respectively, p = 0.026). Conclusion: Our data support the prognostic value of both IPI and FLIPI, with FLIPI demonstrating a more convenient patient distribution among risk classes. A low FLIPI score was also associated with a longer TTF. This might partially contribute to a more favourable prognosis.