Post-marketing data regarding brentuximab vedotin (BV) are sparse. The aim of this study was to assess the frequency and nature of significant adverse drug reactions (ADRs) in patients treated with BV in a real-world setting. We conducted a systematic retrospective study of patients treated with BV in a French university hospital. Significant ADRs were collected using the electronic patient records. Between January 2009 and December 2016, 39 patients received BV. Median age was 43.2 and 53.8% were males. Overall, 20 patients (51.3%) experienced at least one significant ADR and 24 reactions were reported in total. Twelve (50%) out of 24 ADRs were severe. The most frequently observed significant ADRs were peripheral sensory neuropathy and CMV reactivation. ADRs led to drug discontinuation for 4 patients and dose reduction for 6 patients. Only 29.2% of the events were spontaneously reported. Prospective monitoring is needed to better assess BV safety.