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The 2 most common chemotherapy regimens used concurrently with thoracic radiation for patients with unresectable IIIA and IIIB non–small-cell lung cancer (NSCLC) are carboplatin-paclitaxel and cisplatin-etoposide. There are no prospective comparisons of these 2 regimens in this setting.To conduct a systematic review of published trials to compare outcomes and toxic effects between cisplatin-etoposide and carboplatin-paclitaxel in patients with non–small-cell lung cancer receiving thoracic radiation.Studies that enrolled patients with stage III disease receiving radiotherapy (RT) with carboplatin-paclitaxel or cisplatin-etoposide were identified using electronic databases (MEDLINE, EMBASE, and Cochrane library) and meeting abstracts. Trials were excluded if they were phase 1, enrolled less than 10 patients, or included surgical resection. A systematic analysis of extracted data was performed with software using random and fixed effect models. Clinical outcomes were compared using point estimates for weighted values of median overall survival, progression-free survival, response rate, and toxic effects. A 2-tailed t test with a significance level of .05 was used for all comparisons.Overall, 3090 patients were included from 31 studies in the cisplatin-etoposide groups (median age, 61 years; 65% male; 40% squamous histology; median radiation dose, 63.0 Gy), and 3728 patients from 48 studies in carboplatin-paclitaxel groups (median age, 63 years; 65% male; 40% squamous histology; median radiation dose, 64.6 Gy). There was no significant difference in response rates between cisplatin-etoposide and carboplatin-paclitaxel (58% vs 56%; P = .26), respectively. For cisplatin-etoposide vs carboplatin-paclitaxel, there was no significant difference in median progression free survival (12 months vs 9.3 months; P = .20), overall survival (19.6 months vs 18.4 months; P = .40), or 3-year survival rate (31% vs 25%; P = .50). Cisplatin-etoposide was associated with higher grade 3 to 4 hematological toxic effects compared with carboplatin-paclitaxel (eg, neutropenia [54% vs 23%; P < .001] and grade 3/4 nausea/vomiting [20% vs 11%; P = .03]), while rates of grade 3 to 4 pneumonitis (12% vs 9%; P = .12) and esophagitis (23% vs 21%; P = .27) were similar.Cisplatin-etoposide and carboplatin-paclitaxel regimens were associated with comparable efficacy when used with concurrent definitive radiotherapy for patients with stage III unresectable NSCLC. The toxic effect profiles favored the carboplatin-paclitaxel regimen.