Background and objective: Co-morbidities are frequent among patients with interstitial lung diseases (ILD). The objective of this study was to investigate their impact on mortality. Methods: We used the Danish National Patient Registry (DNPR) to identify all patients with a first-time diagnosis of ILD between 1998 and 2010. Patients with ILD were matched 1:4 with controls from the background population. The burden of co-morbidity was assessed using the Deyo–Charlson co-morbidity score (DCcs). Mortality risks were assessed using Kaplan–Meier survival curves, and hazard rate ratios (HRR) for death were estimated using Cox proportional hazards regression models. Results: We identified 10 629 patients with ILD with a corresponding incidence estimate of ILD in Denmark of 17.6 per 100 000 inhabitants (95% CI: 16.5–18.7). Mean age was 72 years and 45.6% of the patients were females. Co-morbidity (DCcs ≥ 1) was present in 30% of the ILD patients and 12% of the controls (P < 0.001). The 5-year survival was 56.0% (95% CI: 54.6–56.6) among ILD patients and 84.0% (95% CI: 83.7–84.4) among controls. HRR for death among patients with ILD was 3.82 for males (95% CI: 3.63–4.02) and 3.85 for females (95% CI: 3.62–4.09) with matched controls as reference. Decreasing survival was seen with increasing DCcs for both groups. The 5-year survival for DCcs = 0 was 61% for ILD and 87% for controls compared with 41% versus 58% for DCcs = 2. Conclusion: Survival was impaired for patients with ILD for all levels of the DCcs, although increasing burden of co-morbidity tended to close the mortality gap.