Interstitial lung disease (ILD) is an adverse event associated with gemcitabine administration. Gemcitabine plus nab-paclitaxel, which is now a first-line chemotherapy regimen for pancreatic cancer (PC), may increase the risk of ILD; however, large-scale clinical data on this are limited. Thus, this study aimed to elucidate the incidence and risk factors of ILD in patients with PC receiving gemcitabine plus nab-paclitaxel. Through the Diagnosis Procedure Combination database, a Japanese nationwide inpatient database with outpatient data, we identified consecutive patients with PC who received gemcitabine-based chemotherapy between July 2010 and March 2019 at 205 hospitals. Competing-risk analysis was used to examine the cumulative incidence and risk factors of ILD. Among the 6163 patients who received gemcitabine plus nab-paclitaxel, we documented 168 patients (2.7%) who developed ILD with cumulative incidence rates (95% confidence intervals [CIs]) of 2.0% (1.6%-2.4%), 2.7% (2.2%-3.1%), and 3.1% (2.6%-3.6%) at 3, 6, and 12 months, respectively. Compared with patients with PC who received gemcitabine monotherapy, those who received gemcitabine plus nab-paclitaxel had an adjusted subdistribution hazard ratio (SHR) for ILD of 1.93 (95% CI: 1.51-2.47). Older age was associated with a high risk of ILD in patients receiving gemcitabine plus nab-paclitaxel (adjusted SHR comparing ≥75 to ≤74 years, 1.61; 95% CI: 1.16-2.24). In conclusion, this study demonstrated the clinical course of gemcitabine plus nab-paclitaxel-associated ILD in patients with PC. When gemcitabine plus nab-paclitaxel is administered to elderly patients with PC, symptoms associated with ILD must be monitored.