Abstract Background Aggregation, fragmentation, and low yield are issues frequently found during the cell culture process of bispecific antibodies (bsAbs), whose inherent complexity likely plays a role in causing these issues. Methods In this study, we made a head-to-head comparison between fed-batch cell culture and intensified perfusion cell culture with a symmetric bsAb case. Results In comparison with the fed-batch culture, a 6.6-fold improvement in integrated viable cell density and a 10.9-fold improvement in volumetric productivity were achieved with the intensified perfusion mode. In addition, a significant decrease in aggregation and fragmentation was observed with the intensified perfusion cell culture. Furthermore, product homogeneity was improved, which was reflected by the increased percentage of capillary isoelectric focusing main group. The quality improvement with intensified perfusion cell culture can be attributed to the shortened product retention in the bioreactor. Conclusions These findings suggest that intensified perfusion cell culture could be a better choice than traditional fed-batch especially for complex molecules like bsAbs. As this is a single case report, future studies on other cases are needed to further confirm the general applicability of this strategy.