We sought to assess the relative effects of individual anaplastic lymphoma kinase (ALK) inhibitors for the treatment of non-small cell lung cancer (NSCLC). We searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (July 23, 2019) for randomized controlled trials (RCTs) that included participants with ALK- or ROS1-positive NSCLC who received any ALK inhibitor compared with placebo, another ALK inhibitor, or the same ALK inhibitor at a different dose. The primary outcome was treatment-related death. Secondary outcomes were overall survival (OS), progression-free survival (PFS), and serious adverse events. Data were pooled via meta-analysis and network meta-analysis, and risk of bias was assessed. PROSPERO: CRD42017077046. Thirteen RCTs reporting outcomes of interest among participants with ALK-positive NSCLC were identified. Treatment-related deaths were rare, with 10 deaths attributed to crizotinib (risk difference v. chemotherapy: 0.49, 95% credible interval CrI -0.16 to 1.46; odds ratio 2.58 (0.76-11.37). All ALK inhibitors improved PSF relative to chemotherapy (hazard ratio 95% CrI: crizotinib 0.46 0.39-0.54; ceritinib 0.52 0.42-0.64; alectinib 300 BID 0.16 0.08-0.33; alectinib 600 BID 0.23 0.17-0.30; brigatinib 0.23 0.15-0.35), while alectinib and brigatinib improved PFS over crizotinib and ceritinib (alectinib v. crizotinib 0.34 0.17-0.70; alectinib v. ceritinib 0.30 0.14-0.64; brigatinib v. crizotinib 0.49 0.33-0.73; brigatinib v. ceritinib 0.43 0.27-0.70). OS was improved with alectinib compared with chemotherapy (HR 0.57 95% CrI 0.39-0.83) and crizotinib (0.68 0.48-0.96). Use of crizotinib (odds ratio 2.08 95% CrI 1.56-2.79) and alectinib (1.60 1.00-2.58) but not ceritinib (1.25 0.90-1.74), increased the risk of serious adverse events compared with chemotherapy. Results were generally consistent among treatment-experienced or naïve participants. Treatment-related deaths were infrequent among ALK-positive NSCLC. PFS may be improved by alectinib and brigatinib relative to other ALK inhibitors; however, the assessment of OS is likely confounded by treatment crossover and should be interpreted with caution.