Few studies have examined the role of IMPT in patients (pts) with stage III non-small cell lung cancer (NSCLC). We report the long-term clinical outcomes and toxicities of IMPT vs. IMRT in pts with stage III NSCLC at our academic institution, which offers proton-based radiotherapy (RT) at two campuses. One hundred sixty-three (163) consecutively treated pts with stage III NSCLC underwent definitive IMPT (21%) or IMRT (79%) from May 2015 to August 2018. Patient, tumor, and treatment characteristics were analyzed with chi-squared testing. Kaplan-Meier survival curves were calculated since starting RT and compared with the log-rank test for overall survival (OS), freedom from distant metastasis (FFDM), and freedom-from local relapse (FFLR). Univariate and multivariate cox regressions were conducted for the final models. Acute (during RT), subacute (3 months), and late (≥6 months) toxicities (CTCAE v4.03) were analyzed. Median follow-up of surviving pts since starting RT was 19.3 (range, 4.6-46) months. For 146 (90%) pts who received 1.8-2 Gy/fraction, the median RT dose was 60 (range, 50.4-72) Gy; 92% of all pts received concurrent chemotherapy. There were no differences in rates of interstitial lung disease (ILD), immunotherapy, biologic therapy, or completion of chemotherapy between the IMPT and IMRT cohorts. However, compared to IMRT, the IMPT pts were more often oxygen-dependent prior to RT (14 vs. 5%, P<0.05) and completed RT less frequently (91 vs. 99%, P=0.03). At 18 months, the IMPT and IMRT cohorts had similar OS (78 vs. 72%, P=0.41), FFDM (72 vs. 61%, P=0.92), and FFLR (90 vs. 88%, P=0.51). On multivariate analyses, more advanced T-stage was associated with inferior FFLR (P<0.01) and FFDM (P<0.01). Pre-treatment COPD (P=0.01) and ILD (P<0.01) were associated with inferior OS. Treatment was well-tolerated with no significant differences in grade ≥ 3 acute (P=0.9), subacute (P=0.8), or late (P=0.4) toxicities between IMPT and IMRT pts. Only 7 (4%) pts had grade ≥ 3 pneumonitis. Two (1%) pts who received IMRT had acute grade 4 pneumonitis. After adjusting for baseline toxicity, pre-treatment ILD was a significant risk factor for developing grade ≥ 3 pneumonitis (odds ratio 5.8, P=0.049). There were no treatment-related grade 5 toxicities. Our long-term experience suggests that IMPT and IMRT have comparable clinical outcomes and toxicity profiles in a large cohort of stage III NSCLC treated at our institution. Poor pulmonary function predicts for RT-related pneumonitis and inferior clinical outcomes. IMPT is a safe and efficacious treatment option for patients with stage III NSCLC, including those with poorer respiratory status. Continued support for the national NRG 1308 trial is desired.