The clinical benefit of second-line chemotherapy in advanced biliary tract cancers is currently unknown. We investigated the role of platinum re-challenge in a selected cohort of patients who progressed after first-line gemcitabine/cisplatin (GemCis) chemotherapy. We retrospectively analysed seventy-four patients treated between January 2008 and September 2012 at Nottingham University Hospitals. Demographics, treatment data, radiological response and survival data were captured. Univariate and multivariate analysis of survival outcomes were evaluated. Platinum sensitive disease was defined as tumours that progress after 12 weeks of completion of first-line GemCis chemotherapy. Seventy-four patients (median age = 67 years) had received first-line chemotherapy (gemcitabine alone = 21/74, Gem/Cis combination = 53/74). Best response to GemCis chemotherapy was as follows; partial response (PR) (17 %), stabilisation of disease (SD) (39.6 %), disease control rate (DCR) (56.6 %) and disease progression (43.4 %). 18/74 patients received second-line chemotherapy [GemCis (12/18), 5-FU/cisplatin (4/18), gemcitabine (2/8)]. Best response to GemCis second-line chemotherapy was as follows: PR (33.3 %), SD (33.3 %) and DCR (66.6 %). The median overall survival in patients who received second-line chemotherapy was 29 months compared to 10.6 months in patients who received first-line therapy only (p = 0.00001). The data suggest that patients who progress after 12 weeks of completion of first-line therapy may remain platinum sensitive and benefit from second-line platinum re-challenge. Prospective multicentre studies are warranted to explore this possibility further.