Background Patients with relapsed or refractory classical Hodgkin lymphoma (R/RcHL) have limited opportunities for a curative therapy. High-dose therapy followed by autologous stem cell transplantation (HDT-ASCT) produces cure rates of 50-60%. Patients relapsing after, or ineligible for HDT-ASCT have limited therapeutic options and long-term remission is uncommon. Furthermore, few patients are candidate to allogeneic stem cell transplantation (AlSCT), a potentially curative approach. The combination of brentuximab-vedotin and bendamustine (BVB) is a promising treatment for patients with R/RcHL, regardless of SCT eligibility. Patients and methods We report a real-life experience with BVB in 41 patients with R/RcHL after failure of ≥1 therapy including ASCT, AlSCT, or BV. Results Among 40 patients evaluable for efficacy, the overall response rate and complete response (CR) rate was 75% and 50%, respectively. No significant differences were observed between primary refractory and relapsed disease, previously treated with ≤2 and ≥3 lines of therapy, or BV-exposed and BV-naïve. After a median follow-up of 38 months, the median progression free survival (PFS) for the entire population is 26 months; PFS is not reached, 10.5 months and 4 months for patients achieving CR, partial response and no response, respectively (p<0,0001). BVB was well tolerated and no grade 4 toxicity or new safety signals were observed. The most common treatment-emergent adverse events were infections. Conclusion Our experience supports the efficacy and tolerability of the BVB combination in R/RcHL as a bridge to SCT or as a definitive therapy for SCT-ineligible patients. Larger comparative studies testing BVB against standards of care are warranted in both settings. MICROABSTRACT In the real-life setting, the combination of brentuximab vedotin and bendamustine was well tolerated and produced an ORR of 75%, CR 50% and a median PFS of 26 months. A significant proportion of heavily pretreated cHL patients may be cured with this approach.