OBJECTIVES: To assess the efficacy and safety of Fluticasone Furoate Nasal Spray (FFNS) for the treatment of Perennial Allergic Rhinitis (PAR) in adults and adolescents. METHODS: We conducted a systematic review with data sought from two electronic databases (MEDLINE and The Cochrane Library) up to August 2017. The population of interest was patients 12 years and older with PAR, previously treated and clinically symptomatic. We limited our selection to phase III or IV, double-blinded randomized controlled trials (RCTs), comparing FFNS, 110 µg once daily, with placebo. Clinical outcomes of interest included the reflective and instantaneous total nasal symptoms scores (rTNSS and iTNSS), the reflective and instantaneous total ocular symptom scores (rTOSS and iTOSS), quality of life (QoL) and adverse events (AEs). To analyze data from the included studies, we performed a meta-analysis using STATA (version 14). RESULTS: Six RCTs (2372 patients) were selected. FFNS produced a statistically significant reduction over placebo in rTNSS (standardized mean difference [SMD] -0.390; 95% CI -0.476 to -0.303, p<0.001) in both the short (less than 6 weeks) and long term (52 weeks or more). A greater improvement was also established in iTNSS (-0.360, -0.484 to -0.236, p<0.001), rTOSS (-0.163, -0.293 to -0.033, p=0.014), iTOSS (-0.165, -0.295 to -0.035, p=0.013) and QoL (-0.322, -0.452 to -0.191, p<0.001) in the short term. All effect sizes were greater than -0.5, indicating small changes according to Cohen’s guidelines. The incidence of most adverse events with FFNS was similar to that with placebo, with the exception of epistaxis, which was more frequent with FFNS in both the short (FFNS 7%, placebo 4%, p=0.004) and long term (FFNS 25%, placebo 13%, p<0.001). CONCLUSIONS: FFNS in adults and adolescents with PAR resulted in statistically significant but not clinically relevant improvements in symptoms and QoL compared with placebo.