OBJECTIVES: In the absence of head-to-head clinical trial data, an indirect comparison of bevacizumab (BEV) versus pemetrexed (PMX) was conducted to compare survival outcomes among adenocarcinoma non-squamous metastatic Non-Small Cell Lung Cancer (mNSCLC) patients. METHODS: An adjusted matched indirect analysis was conducted to estimate overall survival (OS) in adenocarcinoma mNSCLC patients treated with BEV+cisplatin doublet therapy using patient-level data from SAiL (ECCO/ESMO, 2009). These estimates were indirectly compared to previously published survival outcomes for PMX+cisplatin-treated patients (Oncologist 2009;14:253–263) by calculating the median ratio (MR) for OS. A subset of the SAiL population was selected to more closely approximate the PMX population by excluding patients who did not have cisplatin doublet as their baseline treatment, those with a baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) of >=2 and those with non-adenocarcinoma histology. This sample of BEV patients was matched to the adenocarcinoma subgroup from the PMX trial on stage of disease and ECOG PS. One thousand repeated random matched samples of the SAiL data were produced to generate a distribution of survival outcomes and infer a 95% confidence interval (CI) around the mean of all sampled median survival estimates. RESULTS: After adjusted matching, the estimated median OS benefit for BEV patients was 15.6 months (95% CI: 15.0, 16.5) compared to the published median OS of 12.6 months (95% CI: 10.7, 13.6) for PMX patients. BEV patients had longer median OS with an MR of 0.81 (95% CI: 0.71, 0.82). CONCLUSIONS: Results from this indirect comparison show that BEV-based therapy provides superior overall survival outcomes when compared to PMX in adenocarcinoma mNSCLC patients.