Introduction: This final analysis of a long-term extension (LTE) study assessed the safety, tolerability, and effectiveness of peficitinib (ASP015K), a pan-Janus kinase inhibitor, in Asian patients with rheumatoid arthritis (RA). Methods: Patients had previously completed the 12-week phase 2b (RAJ1), or 52-week phase 3 (RAJ3 and RAJ4) peficitinib studies in Japan, Korea, and Taiwan, and received oral peficitinib 50 or 100 mg/day. Dose increase to 150 mg/day or reduction to 50 mg/day was permitted. Efficacy endpoints included American College of Rheumatology (ACR)20/50/70 response rates, 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP), and ACR components. Safety endpoints included treatment-emergent adverse events (TEAEs), and incidence rates (IRs) of adverse events of special interest per 100 patient-years (PY). Results: Overall, 843 patients received peficitinib for a mean 32.0 months (maximum 85.2 months), and most (64.4%) received peficitinib 100 mg/day as a maximum dose. Respective ACR20/50/70 response rates were maintained from baseline (week 0 of LTE; 71.6, 52.1, and 34.7%) to end of treatment (78.7, 63.3, and 44.1%); continuous improvements in ACR components and DAS28-CRP were observed from the baselines of preceding studies and throughout the LTE. Overall, 796/843 (94.4%) patients experienced TEAEs; most were severity grade 1/2. Most common TEAEs were nasopharyngitis (47.0%) and herpes zoster (17.3%). Drug-related TEAEs leading to permanent discontinuation occurred in 140 (16.6%) patients, and IRs (95% confidence interval) per 100 PY of serious infections, herpes zoster-related disease, and malignancies were 2.7 (2.1, 3.4), 7.3 (6.2, 8.6), and 1.2 (0.9, 1.8), respectively. Two deaths occurred during the study; one each from diffuse large B cell lymphoma and pneumonia, which were, respectively considered probably and possibly related to study drug. Conclusions: Improvements in effectiveness variables were maintained during this long-term study of peficitinib in Asian patients with RA; peficitinib was generally well tolerated over a mean 32 months’ duration. Trial Registration: ClinicalTrials.gov. NCT01638013, retrospectively registered on 11 July 2012 https://clinicaltrials.gov/ct2/show/NCT01638013.