Although quality of life (QOL) is one of the most important considerations in patients treated with anticancer therapies, desirable regimens for neoadjuvant chemotherapy including QOL in locally advanced urothelial carcinoma remain unclear. The present study evaluated the influence of neoadjuvant platinum-based chemotherapy on QOL in patients with locally advanced urothelial carcinoma. Between June 2013 and March 2016, 83 urothelial carcinoma patients who received two courses of neoadjuvant chemotherapy were enrolled in this prospective observational study. Neoadjuvant regimens included gemcitabine + cisplatin (GCis) or gemcitabine + carboplatin (GCb) therapies. As a primary endpoint, we assessed QOL changes in each group before and after chemotherapy using the Quality of Life questionnaire on days 1, 3, and 15 of each cycle. Secondary endpoints included toxicity, safety, weight loss, renal function decline, and tumor responses. QOL analyses were performed in 39 patients receiving GCis and in 44 patients receiving GCb. Appetite loss, role functioning, nausea/vomiting, physical, and fatigue deteriorated >10% from baseline in the GCis group but not in the GCb group. Constipation worsened, whereas scores for pain and emotional items improved in both groups. Objective response rates were 38.5 and 43.2% in the GCis and GCb groups, respectively. Both GCis and GCb regimens were feasible in terms of QOL. The GCb regimen may be associated with a better QOL status especially in regard to gastrointestinal symptoms.