Background: Extensive-disease small cell lung cancer (ED-SCLC) is usually first treated with etoposide-/platinum-based chemotherapy. Despite high initial response rates, progression occurs frequently. While topotecan is approved as 2nd-line therapy, further treatment is not standardized. One of the drugs administered in progressed SCLC is paclitaxel. Here, we retrospectively analyzed prognostic factors and outcome of paclitaxel-treated SCLC patients. Methods: SCLC patients treated with paclitaxel between 2005 and 2015 at Thoraxklinik at Heidelberg University Hospital were retrospectively reviewed. Significant prognostic factors were identified by univariate (Kaplan-Meier) and multivariate (Cox-Regression) analysis. Results: 185 patients (119 men/66 women, median age 64 years, median ECOG performance status 1) were included. Paclitaxel was mainly given as 3rd- or 4th-line therapy (92%). The overall response rate was 17% and disease control rate (DCR) was 28%. Median progression-free survival (PFS) was 48 days (95%-CI: 42-54) and median overall survival (OS) 100 days (95%-CI: 84-116). Main toxicities were fatigue (25%) and peripheral neuropathy (17%), but no discontinuation of treatment was required. In 28%, the paclitaxel dose was reduced by 15-30%, mainly due to hematoxicities (in 57%). In univariate analysis, this was linked to a decrease in PFS (p = 0,05), while gender, age, performance status, number of metastatic sites, and presence of cerebral/hepatic metastases were not associated with changes in PFS. For OS, performance status, number of metastatic sites, cerebral/hepatic metastases, and dose reduction were significant (p < 0,05). In multivariate analysis, gender, age, and dose reduction retained as independent prognostic factors for PFS. In addition, performance status, cerebral/hepatic metastases, and pack years were identified as independent prognostic factors for OS. Conclusions: With a DCR of 28% paclitaxel was still effective in heavily pretreated SCLC patients. However, patients should be selected carefully regarding age, performance status, and metastatic status. Especially, patients in good condition and without cerebral/hepatic metastases benefit from a paclitaxel therapy. Legal entity responsible for the study: Martin Steins. Funding: Thoraxklinik at Heidelberg University Hospital. Disclosure: F. Bozorgmehr: Honoraria: MSD, Novartis; Research funding: BMS. S. Rieken: Honoraria and travel expenses: Elekta Inc., Accuray Inc., AstraZeneca GmbH, Bristol-Myers Squibb, Lilly, Roche, DGP, DKG, Degro; IITs and other research funding: Bristol-Myers Squibb, Accuray Inc., Merck KGaA; Consulting or advisory role: Accuray Inc., AstraZeneca GmbH. S. Liersch: Honoraria: MSD, Sanofi; Advisory board: BMS, Amgen, MSD. T. Muley: Research grants: Roche, Chugai Pharma; Travel expenses, patent applications: Roche. M. Thomas: Honoraria: Lilly, BMS, MSD, Roche, Pfizer, AstraZeneca; Advisory boards: Lilly, BMS, MSD, Roche, Pfizer, AstraZeneca, Cellgene, Mediolanum. All other authors have declared no conflicts of interest.