OBJECTIVES: To compare the efficacy and safety of tumour necrosis factor alpha (TNF) inhibitors in the treatment of active ankylosing spondylitis (AS), in adult patients naïve to biologic therapy. METHODS: A literature search was performed, first focused on identifying health technology assessment reports (HTAR), meta-analysis and systematic reviews. The databases searched were MEDLINE, EMBASE, CRD, and the Cochrane Library. An exhaustive search of randomized controlled trials (RCTs) that compared directly the TNF-inhibitors was also carried out in MEDLINE and EMBASE. Both searches covered until November 2010. Two authors independently selected the studies, assessed the quality, and performed the data extraction, with disagreements resolved by a third reviewer until consensus was obtained. In addition, an analysis of adjusted indirect comparisons (AIC) against a common comparator was done using the method of Bucher et al. and the software from the Canadian Agency for Drugs and Technologies in Health version 1.0. RESULTS: A HTAR was included, it compared the clinical efficacy of infliximab, etanercept and adalimumab associated with conventional treatment versus conventional treatment and it also compared TNF-inhibitors between them. Five RCTs were included to update the report. One study directly compared infliximab and etanercept and the other four RCTs evaluated each of the TNF-inhibitors (infliximab, etanercept, adalimumab and golimumab) versus placebo. In the AIC analysis performed considering all the evidence available, no statistically significant differences in the ASAS20 response between infliximab, etanercept, adalimumab and golimumab were found. Also, there were no statistically significant differences between the TNF-inhibitors in the rate of serious infections or withdrawals due to adverse events. CONCLUSIONS: Only one RCT directly compares two TNF inhibitors. Therefore, in the absence of such trials, AIC are considered. No clinically relevant differences are observed in the efficacy and safety between infliximab, etanercept, adalimumab and golimumab in the treatment of adult patients with AS.