There is concern that patients with collagen vascular disease (CVD) are at higher risk of developing radiation toxicity. We analyzed radiation toxicities in patients with intrathoracic malignancy and CVD treated using modern radiotherapy.This single-institution retrospective study included 31 patients with CVD and 825 patients without CVD treated from 1998 to 2014. Radiation esophagitis (RE) and radiation pneumonitis (RP) were scored by RTOG scales. RE was analyzed with logistic regression and RP with Cox regression.CVD patients experienced similar grade ≥3 RE compared to control patients (23% vs. 19%, p = 0.64) but more grade ≥3 RP (26% vs. 10%, p = 0.01). There was no significant association between CVD subtype and toxicities. In multivariate analysis, CVD and lung V20 >30% were associated with grade ≥3 RP. We identified V20 ≤30%, V5 ≤50%, and MLD ≤18 Gy as dose thresholds in patients with CVD. CVD patients with mild severity disease and only 1 organ system involved were at low risk for RP.Patients with CVD may be at higher risk of RP. However, CVD patients may be offered curative thoracic RT with particular attention to risk-reduction strategies and maintaining recommended dose constraints as described in this study.