OBJECTIVE To assess the effect of adjuvant chemotherapy on the postoperative survival of patients with transitional cell carcinoma of the bladder and lymph node involvement and/or lymphovascular invasion (LVI). METHODS We retrospectively analyzed the data from 260 patients who had undergone radical cystectomy for transitional cell carcinoma of the bladder. Of these 260 patients, 85 (33%) had nodal involvement and 125 (48%) had LVI. Chemotherapy, consisting of three to six cycles of either methotrexate, vinblastine, cisplatin, and doxorubicin or gemcitabine and cisplatin, was administered to 17 (26.6%) of 64 patients with pT3-4N0 disease and 43 (50.6%) of 85 patients with node-positive disease. We determined the factors influencing cancer-specific survival and the effect of chemotherapy according to pathologic stage, LVI, and nodal status. The mean follow-up was 43.8 months (range, 3 to 180; median 33.6). RESULTS The overall 5-year cancer-specific survival rate was 65.6%. When we considered nodal involvement and LVI simultaneously, the 5-year survival rate was 92.2% for the node and LVI-negative patients, 60.7% for the node-negative but LVI-positive patients, and 32.5% for the node-positive patients. Chemotherapy was beneficial in the node-positive patients (5-year survival rate of 37.4% versus 26.9%; P = 0.0035) but not beneficial in the node-negative patients, regardless of LVI status. When subclassifying node-positive patients with regard to N stage or LVI status, the effect of chemotherapy was limited to those with Stage N2 (P = 0.002) or LVI-positive status (P = 0.001). CONCLUSIONS Adjuvant chemotherapy would be beneficial in patients with node-positive transitional cell carcinoma, especially those with a high nodal disease burden (Stage N2) or LVI, after radical cystectomy.