Exhaled nitric oxide (FeNO) is a marker for airway inflammation measured by hand-held or stationary analyzers, but their usability was not previously assessed. NIOX VERO (CN), NObreath (BN), Vivatmo pro (BV), and CLD88 analyzer (reference, EC) were compared in a prospective study of the general population LEAD (Lung, hEart, sociAl, boDy) cohort, including the System Usability Scale and tests for equivalence at a clinically relevant range of ≤ 70 ppb with linear models and Bland-Altman plots. In 486 participants (62.4 ± 14.2 years old, 48.1% female), all hand-held analyzers had a good usability score, with BN scoring best. BV required the fewest attempts and time to measurement success, followed by BN. The FeNO results were clinically equivalent between devices (difference to EC 0.7-7.5 ppb) with increasing variability at higher FeNO values. The analyzers had an agreement of ≥ 95% at the threshold of ≥ 40 ppb. CN showed the lowest difference to EC, followed by BV. All portable analyzers showed good usability with an above-average usability score. The best usability score was observed with the BN device, while the BV device had the shortest measuring time and the fewest additional attempts. The lowest difference to the stationary EC analyzers was observed with the CN device.