The aim of this multi-center retrospective study was to clarify the prognostic factors for respiratory-related death in patients with rheumatoid arthritis (RA) complicated interstitial lung disease (ILD). Patient background data, treatment regimen, and disease activity indicators of RA and ILD at baseline, 6 months after diagnosis of ILD, and at the last follow-up visit were extracted. A total of 312 patients with RA-ILD (17 patients who died from respiratory-related causes and 295 survivors) were included. Patients who died from respiratory-related causes had an older median age, higher proportion of males, and a higher anti-cyclic citrullinated peptide antibody positivity rate than survivors (P = 0.0001, 0.038, and 0.016, respectively); they also had significantly higher baseline serum levels of KL-6 than survivors (P = 0.013). Patients who died from respiratory-related causes showed significantly greater changes in serum KL-6 levels between the six-month timepoint and the last visit (ΔKL-6 [6 m-last]) than survivors (P = 0.011). Multivariate analysis showed that the ΔKL-6 (6 m-last) corrected by disease duration was a predictor of respiratory disease-related death in patients with RA-ILD (P <0.0001). Long-term increase in serum KL-6 levels is associated with respiratory disease-related death in patients with RA-ILD.