Introduction Use of fractional exhaled nitric oxide (FeNO) is recommended for asthma diagnosis but its role in guiding safe reduction of inhaled corticosteroids (ICS) is unclear. Aims and objectives To assess the value of FeNO in identifying asthma patients in whom ICS can be safely reduced. Methods We performed a systematic electronic database search to identify studies which recruited asthma patients aged >=12 years maintained on low to moderate dose ICS in whom FeNO was measured at baseline before subsequently stepping down ICS treatment, irrespective of what the baseline FeNO value was. We performed multi-level mixed-effects logistic regression in relation to absence or presence of acute exacerbations up to 12 weeks after stepping down ICS, accounting for withinstudy clustering, age, sex and FeNO as baseline covariates. FeNO was categorised as low (<=20 ppb [parts per billion]), intermediate (>20 ppb to <50 ppb) or high (>=50 ppb). Net benefit values were calculated for ICS step-down guided by FeNO versus stepping down ICS in all patients or no patients for baseline exacerbation risk thresholds up to 30%. Results We obtained individual patient data from seven studies (393 patients; acute exacerbation, n=44). After adjustment for all baseline covariates in our regression model, exacerbation risk was significantly higher in patients with high FeNO (odds ratio [OR] 2.70, 95% confidence interval 1.16 to 6.26, p=0.021) than low FeNO. FeNO-guided step-down decisions had greater net benefit than stepping down treatment in all patients or no patients at baseline exacerbation risk thresholds between 6% and 16%. Conclusion Patients with mild-to-moderate asthma whose FeNO is >=50 ppb are at greater risk of exacerbation following ICS reduction than patients whose FeNO is in the low or intermediate range. Assessment of FeNO is therefore important in guiding safe clinical decisions about stepping down treatment in asthma patients who appear to be symptomatically controlled on low or moderate dose ICS.