Severe acute esophagitis (AE), grade (G) ≥3 by CTCAE, occurs in ∼7-21% of locally advanced NSCLC or SCLC patients (pts) treated with concurrent chemo/radiation therapy (CRT) to ≥60 Gy once-daily. G3+ AE represents a dose-limiting toxicity and is associated with poor treatment outcomes, as shown in RTOG 0617. We hypothesized that formalized sparing of the contralateral esophagus (CE) reduces the risk of severe AE by preserving partial organ functionality. We performed a phase I clinical trial to prospectively test an empirically developed CE-sparing technique on an IRB-approved protocol (registered with clinicaltrials.gov). Pts with locally advanced NSCLC (+/- solitary brain metastasis) or limited-stage SCLC with gross tumor within 1 cm of the esophagus were eligible. Pts were treated with IMRT or VMAT and daily CBCT to 70 Gy at 2 Gy/fraction. The PTV was a uniform 5 mm expansion. The esophageal wall contralateral to gross tumor was contoured as an avoidance structure to guide a steep dose falloff gradient across the esophagus, except on slices where tumor surrounded the esophagus. Target coverage was always prioritized over CE sparing, and 99% of ITV and PTV were covered by 70 Gy and ≥63 Gy, respectively. To be analyzable for the primary endpoint of G3+ AE (CTCAE v4), pts needed to have received concurrently ≥5 cycles of weekly carboplatin/paclitaxel or ≥2 cycles of platinum + pemetrexed or etoposide and have had ≤3 days of unplanned treatment interruption unrelated to esophagitis. Survival times were calculated from date of registration. Of 27 pts accrued between 7/2015 and 1/2019, 25 completed treatment and were analyzable for secondary endpoints while 20 were analyzable for the primary endpoint (analysis was performed with complete follow-up until February 9, 2020). Median age was 67 years (range, 51-81 years). There were 15 males and 10 females. Nineteen pts had NSCLC and 6 had SCLC. AJCC stage (7th ed.) distribution was: IIIA 52%, IIIB 40%, IV 8%. Total dose was 70 Gy (n = 24) or 68 Gy (n = 1). Median esophagus V60 was 11% (1-29%). Median CE max dose, V55, and V45 were 66 Gy (44-71 Gy), 1.4cc (0-5.3cc), and 2.7cc (0-9.2cc), respectively. Median follow-up was 33.3 months (11.1-52.2 months). The rate of G3+ AE was 0%. Other radiation-related toxicities were: G2 AE 25%, G2+ pneumonitis 12% (G2 n = 2, G5 n = 1), G3+ cardiac toxicity 8% (G3 n = 1, G5 n = 1). There was no isolated local tumor failure. Two-year overall survival rate was 67% (95% CL, 45-82%), and median progression free-survival time was 25.9 months (95% CL, 11.2 to not reached). CE sparing is associated with substantially reduced AE in CRT pts treated to 70 Gy, with no G3+ AE despite gross tumor within 1 cm of the esophagus. We hypothesize that contralateral wall sparing converts the esophagus from a serial to a parallel organ, a concept that may be readily adaptable into clinical practice.