BACKGROUND Crizotinib show a promising efficacy in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). However, differences in efficacy for first- and second-line crizotinib are unclear. RESULTS The pooled overall response rate and progression-free survival were 65% and 9.38 months, respectively. In the subgroup analysis, first-line crizotinib showed a higher trend of overall response rate and longer trend of progression-free survival although there was no statistical difference between first-line and second-line crizotinib (74%, 11.28 months vs. 65%, 8.12 months, respectively; fixed effects model). Moreover, overall response rate between Asians and Caucasians were similar (67% and 66%, respectively; fixed effects model). MATERIALS AND METHODS A comprehensive search of MEDLINE, EMBASE, WEB OF SCIENCE and the COCHRANE databases from their inception to February 2016 was performed to identify clinical trials in English-language journals. Pooled overall response rate, progression-free survival and differences between first- and second-line crizotinib were estimated. Moreover, overall response rate between Asians and Caucasians were also estimated. CONCLUSIONS First-line crizotinib may more effective than second-line crizotinib for patients with locally advanced or metastatic ALK-positive NSCLC.