Background: NHL survivors are at high risk for second cancers (SC) and late toxicities such as cardiovascular (CV) or neuro-psychiatric (NP) disorders. Little is known about new agents such as rituximab (RITUX). The impact of treatment regimens on late morbidity was analyzed in a large cohort of survivors with long follow-up (FU). Methods: In 2015, a fatigue (MFI-20) and a self-assessment Life Situation Questionnaire (LSQ) were mailed to survivors treated in 12 successive LYSA randomized trials (1993-2007) for Diffuse Large B cell (DLBCL) and follicular (FL) lymphomas. Of 8113 pts enrolled into trials, 5247 were alive at last FU. Addresses were obtained for 3317 survivors of whom 1671 (50%) returned the questionnaires. Responders more often came from recent trials and were more often treated with RITUX than non-responders. NHL prognostic factors and chemotherapy were similar in both groups. Linear regression models were used to assess factors linked to increased fatigue level. Results: There were 906 males and 765 females (median age 64 yrs; 24 to 95). 28% had FL and 72% DLBCL. 811 pts received CHOP-like chemotherapy, 518 high-dose CHOP and 342 up-front autograft consolidation (ASCT). RITUX was combined to chemotherapy in 829 pts (50%). Median FU was 11 yrs (5 to 23). 583 pts (35%) reported no morbidity. For the remaining, late events (1 to 7) were: CV in 20%, NP in 17%, infections in 12%, musculoskeletal (MSk) disorders in 11%, pulmonary (Pulm) diseases in 8%, digestive diseases in 5% and SC in 8%. RITUX was associated with less SC (6 vs 9%, p = 0.02) and less CV (17 vs 23%, p = 0.006). Up-front ASCT was associated with more infections (17 vs 11%, p = 0.002) and more Pulm (12 vs 7%, p = 0.005). Age above 75 (20%) was only associated with more CV and more SC. 1036 pts (64%) expressed persistent fatigue (MFI score ≥ 40). There were no significant impact of any treatments. Increased fatigue level was associated (p < 0.001) with age, obesity, CV, Pulm, MSk and NP. Conclusions: This first study reporting on long-term NHL survivors confirmes an altered health status. Initial combination of chemotherapy and RITUX does not increase late morbidity and fatigue. Clinical trial information: pooled trials already registred.