Background BC2001 demonstrated improved local control with the addition of chemotherapy to radiotherapy in 360 patients with muscle-invasive bladder cancer. Objective To establish whether such benefit remained in BC2001 patients who received prior neoadjuvant chemotherapy. Design, setting, and participants A total of 117 patients (33%) received neoadjuvant chemotherapy and were randomised to radiotherapy with (48%) or without (52%) concomitant chemotherapy. Patients were recruited between August 2001 and April 2008 from 28 UK centres. Intervention Platinum-based neoadjuvant chemotherapy, followed by radiotherapy with (cRT) or without (RT) synchronous 5-fluorouracil and mitomycin-C. Outcome measurements and statistical analysis Toxicity, locoregional control (LRC), overall survival (OS), and quality of life (QoL) were measured. Results and limitations Of the patients, 74% received gemcitabine plus cisplatin or carboplatin. Compliance rates with full-dose radiotherapy were cRT 93% and RT 92%. An excess of grade ≥3 toxicities while on (chemo)radiation occurred for cRT 33% versus RT 22%, although nonstatistically significant (p = 0.16). With 110 mo median follow-up for survival (interquartile range 96–123), cRT showed improved LRC though not statistically significant (adjusted hazard ratio [aHR] = 0.64, 95% confidence interval [CI] 0.33–1.23, p = 0.18). No differences in OS (aHR = 0.95, 95% CI 0.57–1.57, p = 0.8) were observed. No significant detriment in QoL was observed between cRT and RT in this subgroup of patients. Conclusions Neoadjuvant chemotherapy does not compromise the delivery of radical curative treatment. Although underpowered due to a small sample size, the benefit of chemoradiotherapy to improve local control in this group of patients receiving neoadjuvant chemotherapy is consistent with that observed in the main trial. Although a nonsignificant excess of toxicity was observed, there was no evidence of impaired QoL. Patient summary Chemotherapy before radical chemo(radiotherapy) is feasible and well tolerated.