Background: Intranasal corticosteroids (INCSs) are well established in the treatment of allergic rhinitis, chronic rhinosinusitis, and nasal polyposis. Although reversible atrophy of keratinized skin is seen with corticosteroids, the respiratory mucosa is histologically very different and but concerns remain among patients and some health-care professionals over local side effects on nasal respiratory mucosa. A systematic review and meta-analysis were performed of the available evidence for nasal mucosal atrophy as an adverse effect of INCSs in patients with sinonasal disease. Methods: A systematic search of Embase (1974-) and Medline (1946-) databases to September 27, 2013 was performed. Inclusion criteria selected any study where the histopathology of nasal mucosa was assessed in patients with sinonasal disease using intranasally administered corticosteroids with or without a control group. Results: Twenty-three hundred sixty-four publications were retrieved with a subsequent full text review of 149 publications for 34 articles that met the selection criteria. These articles included 11 randomized controlled trials, 5 cohorts, and 20 case series. Duration of treatment varied from 5 days to 5.5 years. "Mucosal atrophy" as an outcome was reported in 17 studies. The definition of "mucosal atrophy" was highly variable with a definition given in only 10 studies. One hundred thirty-six patients were represented in controlled studies of atrophy with only one study reporting the event in both groups with an odds ratio of "mucosal atrophy" at 0.51 (95% CI, 0.09 -3.11; p = 0.47). Conclusion: The concept of nasal mucosal atrophy is poorly defined and there is no histological evidence for deleterious effects from INCS use on human nasal mucosa.