To compare the effectiveness of different taxane-containing regimens and to identify the best strategy for the treatment of human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Network meta-analysis of 20 randomized controlled trials (RCTs). A total of 6577 patients with HER2-negative MBC who received treatment (20 different regimens) with taxanes (paclitaxel [4267 patients] or docetaxel [2310 patients]). The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched (through March 2019) for RCTs that evaluated any taxane-containing regimens for the treatment of HER2-negative MBC. A network meta-analysis in a Bayesian framework was performed using the random-effects model. We compared the surface under the cumulative ranking (SUCRA) curve for each regimen. Overall, paclitaxel-based combinations were superior to paclitaxel alone in objective response rate (ORR) (odds ratio 1.60, 95% credible interval [CrI] 1.15-2.16) and overall survival (OS) (hazard ratio 1.08, 95% CrI 1.01-1.15). Docetaxel-based combinations were also superior to paclitaxel alone in ORR. Among the paclitaxel-based regimens, based on the results of SUCRA, paclitaxel + bevacizumab + capecitabine was likely to be the most efficacious in improving ORR, OS, and progression-free survival (PFS), whereas paclitaxel + gemcitabine was likely to be the most efficacious in 1-year OS rate. Among the docetaxel-based regimens, based on the results of SUCRA, docetaxel + gemcitabine was likely to be the most efficacious in improving PFS and OS. These findings demonstrated that paclitaxel-based combinations can provide significant improvement in ORR and OS compared with paclitaxel alone. The regimens of paclitaxel + bevacizumab + capecitabine, docetaxel + gemcitabine, and paclitaxel + gemcitabine may be superior to other regimens for the treatment of HER2-negative MBC. © 2019 Pharmacotherapy Publications, Inc.