Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare disease. It differs from Classic Hodgkin lymphoma histologically, biologically and clinically, with a more indolent course, a tendency to late relapses and transformation into high-grade B cell lymphomas. There is no consensus on the best treatment approach. The aim of this study is to characterize the clinical characteristics, first-line therapy, outcomes and prognostic factors of NLPHL in our country. We conducted a multicentric, retrospective analysis of patients (pts) with NLPHL diagnosed between 2003 and 2020 in 11 hemato-oncology centers, with a minimum follow-up (FU) of 1y. Overall and complete response rate (ORR and CRR) were defined according to Lugano criteria. Progression-free (PFS) and overall (OS) survival were analyzed using Kaplan-Meier method. Among 140 pts identified, median age at diagnosis was 40y with 69% males, 30% of pts had advanced disease (stage III-IV), 34% ≥3 nodal areas involved, 11% B symptoms and 24% increased LDH. Detailed histological characterization was available in 68 pts, most having the typical variants (A or B). In 19 pts (14%) a “watch and wait” (WW) strategy was chosen; of these, 42% required treatment after a median of 30 mo, while 58% are still under WW at last FU. In the remaining 121 pts, radiotherapy and combined modality treatment (33% and 34% respectively) were used in localized disease, while chemotherapy-only was utilized in 71% of advanced stages, mostly ABVD (42%). Rituximab was associated in 21% of pts, mainly with CHOP and CVP. ORR was 83% and CRR 81%. In localized and advanced disease ORR was 94% and 65% respectively. With a median FU of 65m (95% CI, 55-75) 17 pts relapsed and 8 transformed into high-grade B cell lymphoma. At relapse, salvage chemotherapy with ASCT and chemotherapy with rituximab were equally used. The median number of treatment lines was 1. Five-year PFS and OS were 73.8% (95% CI, 66.4-82.1) and 94.1% (95% CI, 90.0-98.5) respectively. PFS was lower in advanced stages and in pts with ≥3 nodal areas (p<0.001). At last FU 91% of patients were still alive, with 10 deaths (6 lymphoma related). Our study confirms the good outcomes and prolonged survival of NLPHL. Few pts had histological variant characterization, which is increasingly recognized as potentially contributing to better define prognosis and treatment in advanced stages. Treatment strategies should be adequately defined to optimize efficacy and minimize toxicity.