Background <p>Gemcitabine (GEM) + nanoparticle albumin-bound paclitaxel (nab-PTX), which is effective in treating pancreatic cancer, frequently induces peripheral edema. Hypoalbuminemia causes generalized peripheral edema and occasionally occurs in patients with cancer, but reports evaluating its interaction with chemotherapy-induced symptoms are lacking. Therefore, we aimed to assess the effect of baseline hypoalbuminemia on peripheral edema following real-world GEM + nab-PTX therapy.</p> Methods <p>Patients with pancreatic cancer receiving GEM + nab-PTX (n = 212) were divided into a hypoalbuminemia group (serum albumin levels &lt; 3.5&#xa0;g/dL), and a control group without hypoalbuminemia, and retrospectively evaluated. The primary endpoint was the incidence of grade ≥ 2 peripheral edema within 6&#xa0;months of treatment initiation.</p> Results <p>The incidence of grade ≥ 2 peripheral edema within 6&#xa0;months was 5.7% in the control group and 22.6% in the hypoalbuminemia group, with a significant difference (<i>P</i> = 0.0009), meeting the primary endpoint. The onset time of grade ≥ 2 peripheral edema was significantly earlier in the hypoalbuminemia group than in the control group (<i>P</i> = 0.0003). In contrast, the incidence of all-grade symptoms was 20.1% in the control group and 30.2% in the hypoalbuminemia group, which was not significantly different (<i>P</i> = 0.13). These results were confirmed in the propensity score-matched population. Multivariate Cox proportional hazard regression analyses showed that baseline hypoalbuminemia was a significant risk factor for grade ≥ 2 peripheral edema (adjusted hazard ratio, 3.84; 95% confidence interval, 1.60–9.23; <i>P</i> = 0.003).</p> Conclusion <p>Our study revealed that patients with baseline hypoalbuminemia who received GEM + nab-PTX therapy for pancreatic cancer developed problematic peripheral edema.</p>