Introduction: Drug-resistant TB (DR-TB) care shifted from centralized to decentralized care in Tanzania in 2015. This study explored whether DR-TB training and mentoring supported healthcare workers' (HCWs) DR-TB care performance.Methods: This mixed study assessed HCWs' DR-TB care knowledge, the training quality, and the mentoring around 454 HCWs who were trained across 55 DR-TB sites between January 2016 and December 2017. Pre- and post-training tests, end-of-training evaluation, supervisor's interviews, DR-TB team self-assessment and team focus group discussion were conducted among trained HCWs. Interim and final treatment results of the national central site and the decentralized sites were compared.Results: HCW's knowledge increased for 15-20% between pre-training and post-training. HCWs and supervisors perceived mentoring as most appropriate to further develop their DR-TB competencies. Culture negativity after 6 months of treatment was similar for the decentralized sites compared to the national central site, 81% vs 79%, respectively, whereas decentralized sites had less loss to follow-up (0% versus 3%) and fewer deaths (3% versus 12%). Delays in laboratory results, stigma, and HCWs shortage were reported the main challenges of decentralized care.Conclusions: Training and mentoring to provide DR-TB care at decentralized sites in Tanzania improved HCWs' knowledge and skills in DR-TB care and supported observed good interim and final patient treatment outcomes despite health system challenges. [ABSTRACT FROM AUTHOR]