Background <p>Ramucirumab with either solvent-based or nanoparticle albumin-bound paclitaxel is a standard second-line treatment for advanced gastric cancer. Reportedly, nanoparticle albumin-bound paclitaxel has activated the immune system, but the efficacy of taxane-based agents before nivolumab remains unclear. Therefore, we investigated the prognostic effect of ramucirumab with solvent-based or nanoparticle albumin-bound paclitaxel as second-line therapy, followed by nivolumab as third-line therapy.</p> Methods <p>This retrospective study enrolled 115 patients with gastric cancer treated with ramucirumab in combination with <i>solvent-based paclitaxel</i> or nanoparticle albumin-bound paclitaxel from 2017 to 2019 at six hospitals. All patients received nivolumab as a third-line therapy. Ramucirumab + solvent-based paclitaxel and ramucirumab + nanoparticle albumin-bound paclitaxel were administered to 57 and 58 patients, respectively.</p> Results <p>The progression-free survival of the ramucirumab + solvent-based paclitaxel group was slightly better than that of the ramucirumab + nanoparticle albumin-bound paclitaxel group but with no statistically significant difference (5.3&#xa0;months vs. 4.2&#xa0;months). Contrary, the overall survival of the ramucirumab + nanoparticle albumin-bound paclitaxel group was slightly better than the ramucirumab + solvent-based paclitaxel group but with no statistically significant difference (19.0&#xa0;months vs. 12.5&#xa0;months). The multivariate analysis of progression-free survival revealed that ramucirumab + nanoparticle albumin-bound paclitaxel was an independent risk factor for poor prognosis, whereas ramucirumab + nanoparticle albumin-bound paclitaxel was an independent factor for good overall survival.</p> Conclusions <p>Ramucirumab + nanoparticle albumin-bound paclitaxel may prolong overall survival when administered before nivolumab, despite its limited effect on progression-free survival.</p>