Tolerability issues including acne, nausea, and headache have been reported with Janus kinase (JAK) inhibitors for moderate-to-severe atopic dermatitis (AD). To report outcomes of tolerability adverse events (AEs) for baricitinib, a JAK1/JAK2 inhibitor, in patients with moderate-to-severe AD. Acne, headache, and gastrointestinal AEs are reported from placebo-controlled and long-term extensions of pooled data in the baricitinib AD clinical trial program. Proportions of patients with AEs, incidence rates (IRs)/100 patient-years at risk, and median time to onset/duration of AEs were calculated. In 2531 patients treated with baricitinib, most AEs were mild to moderate in severity. Headache was the most common AE of tolerability (median of 14-26 days after first dose of baricitinib, lasting ≤3 days). IRs of acne were <5 in any group lasting up to a median of 90 days with no severe AEs. Diarrhea was the most common gastrointestinal AE, lasting a median of ≤7 days. There were few study drug interruptions (n = 6) and permanent discontinuations (n = 5) for tolerability AEs. For the AEs of tolerability analyzed, baricitinib appears to be well tolerated. Overall, the frequency of these AEs in patients being treated for moderate-to-severe AD was low with few leading to study drug interruption or permanent discontinuation. NCT02576938; NCT03334396; NCT03334422; NCT03428100; NCT03435081; NCT03733301; NCT03334435; NCT03559270 Capsule summary In 2531 baricitinib-exposed patients with moderate-to-severe atopic dermatitis, headache was the most common adverse event (AE) of tolerability. Across all AEs, the majority were mild to moderate in severity. There were few study drug interruptions (n = 6 in all patients who received baricitinib) or permanent study drug discontinuations (n = 5) due to AEs of tolerability, and baricitinib was generally well tolerated.