Background Management of superior sulcus non-small cell lung cancer (NSCLC) continues to evolve, with preoperative chemoradiotherapy (CXRT) followed by surgical intervention supported by several studies. Rates of pathologic complete response (pCR) have varied, and previous attempts to identify clinical predictors of pCR have been unsuccessful. We analyzed our experience with resected superior sulcus NSCLC to elucidate clinical features suggestive of pCR among patients after preoperative treatment. Methods A multiinstitutional retrospective review was performed in patients who underwent resection for superior sulcus NSCLC between January 1988 and July 2013. Data pertaining to comorbidities, staging, therapy, imaging, and outcomes were collected. Logistic regression was performed to identify predictors of survival and pCR. Results During the study, 102 patients underwent preoperative therapy, consisting of CXRT in 75 (73.5%), chemotherapy in 15 (14.7%), and radiotherapy in 12 (11.8%). After median follow-up of 18.0 months, overall and disease-free survivals were 51.0% and 45.1%, respectively. On multivariate regression, independent predictors of survival included pCR (p = 0.001; hazard ratio [HR], 0.243; 95% confidence interval [CI], 0.106-0.555) and age (p = 0.007; HR, 1.049; CI, 1.013-1.085). Among those who received CXRT, 24 of 75 (32%) achieved pCR. Multivariate regression analysis of the CXRT group revealed that pCR was independently predicted by extent of size reduction on imaging (p = 0.015; HR, 1.042; CI, 1.008-1.078), with histologic examination showing a trend toward significance (p = 0.073). Conclusions Preoperative chemoradiation frequently resulted in pCR, and treatment response on imaging was associated with the likelihood of achieving pCR. Future investigations are warranted to further predict pCR from preoperative clinical variables such as symptom resolution, as identification of accurate predictors may ultimately permit the application of selective surgical intervention in superior sulcus NSCLC.