In 2018, the National Cancer Institute of Naples has launched the GLUBREAST Trial to verify the efficacy of cyanoacrylate sealing glue to reduce seroma after axillary dissection in breast surgery. The glue is a synthetic sealant, CE approved for internal human uses and surgical procedures. The assumed mechanism of action in breast surgery is that the glue create a seal coating in the operative field to occlude lymphatic leaks and limit seroma formation. Methods The trial included one hundred-eighty patients scheduled for breast conserving surgery or total mastectomy without reconstruction.Ninety-one were randomized to receive suction drain and sealant glue after axillary dissection (Experimental Arm), whereas eighty-nine patients (Control Arm) received suction drain without glue. Statistics A multivariable mixed effect model on presence of liquid drained and volume drained were calculated. Stratified models by visits were performed. Results The trial ended in June 2022. Older age was associated with a higher volume of seroma drained per day (β 0.30; 95% CI: 0.00‐0.60). 5‐U increase in Body Mass Index was associated with higher daily drained seroma volume in patients underwent breast conserving surgery (β 5.0; 95% CI: 0.62‐9.4), but not in patients underwentmastectomy (β 2.5; 95% CI: ‐3.6‐8.6). We did not find statistically significant differences in presence of liquid drained and volumedrained among the study groups. An advantage for the Experimental Arm was observed from 3 th and 4 th to 5 th outpatientvisits without reaching a statistical significance (p=0.069 and p=0.072, respectively), so far 5% of patients in the ExperimentalGroup had clinical benefit from the glue.Conclusions. Data in the literature come from case series, and surgeons need higher levelof evidence to drive surgical decision-making and choose proper devices to increase patient quality of life. GLUBREAST randomized trial tested the efficacy of cyanoacrylate sealing glue to prevent post-operative seroma in breast surgery. Although only a small number of patients benefited from sealant application, we regret to say this trial has some limitation, i.e. the prolonged presence of suction drain. Further research is warranted to better clarify the benefit of cyanoacrylate glue in breast surgery.