Objective To analyze the efficacy and safety of antibody-drug conjugates（ADCs） combined with programmed cell death 1（PD-1） inhibitors in neoadjuvant therapy for bladder cancer in real-world settings. Methods A retrospective study was conducted on 29 patients with bladder cancer who received ADC combined with PD-1 inhibitors or gemcitabine/cisplatin as neoadjuvant therapy at The First Affiliated Hospital of Chongqing Medical University between August 2017 and December 2023. The patients were divided into Group A（disitamab vedotin combined with atezolizumab） and Group B（gemcitabine combined with cisplatin）. The pathological complete response rate and pathological downstaging rate were compared between the two groups. The adverse events that occurred during treatment were evaluated. Results Group A included 17 patients，among whom 13 patients underwent radical cystectomy，and 4 patients opted for bladder-preserving surgery. Group B included 12 patients，all of whom underwent radical cystectomy. The pathological complete response rate was 41.2% in Group A and 25.0% in Group B（P=0.449）. The pathological downstaging rate was 58.8% in Group A and 50.0% in Group B（P=0.716）. Common adverse events in Group A included abnormal liver function（10 cases，58.8%），peripheral sensory neuropathy（8 cases，47.1%），and anemia（7 cases，41.2%），with 6 cases（35.3%） experiencing grade 3-4 AEs. In Group B，common adverse events included anemia（9 cases，75%），neutropenia（8 cases，66.7%），and nausea（8 cases，66.7%），with 3 cases（25.0%） experiencing grade 3-4 adverse events. Conclusion In neoadjuvant therapy for bladder cancer，ADC（disitamab vedotin） combined with PD-1 inhibitor（atezolizumab） has higher pathological complete response rate and pathological downstaging rate compared to the traditional gemcitabine/cisplatin regimen. Additionally，its safety profile is manageable，and it demonstrates good efficacy in human epidermal growth receptor 2-negative patients.