Background: This study aimed to determine the extent and associated factors of past 6-month reporting of artemisinin-based combination therapy (ACT)-failure by healthcare professionals (HCPs); and difficulties and solutions to the pharmacovigilance (PV) of ACT therapeutic ineffectiveness.Methods: Survey of 685 HCPs from June to July 2018 in purposively selected public and private health facilities in Uganda.Results: One in five [20%, 137/685; 95% confidence intervals (CI) 17% to 23%] HCPs

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... ed ACT-failure to any authority in the previous 6-months. HCPs commonly reported ACT-failure to immediate supervisors (72%, 106/147), mostly verbally only (80%, 109/137); none had ever reported a written ACT-failure to Uganda's National Pharmacovigilance Centre. Common difficulties to reporting ACT-failure were; unavailability of reporting procedures (31%, 129/421), poor follow-up of treated patients (22%, 93/421) and absence of reporting tools (16%, 68/421). Factors associated with reporting ACT-failure in past 6-months were: hospital-status (vs other; OR = 2.4, 95% CI, 1.41 to 4.21), HCPs aged under 25 years (OR = 2.2, 95% CI, 1.29 to 3.76), suspicion of ACT-failure in past 4-weeks (OR = 2.3, 95% CI, 1.29 to 3.92), receipt of patient-complaint(s) of ACT-failure in past 4-weeks (OR = 2.9, 95% CI, 1.62 to 5.12) and HCPs from northern (vs central; OR = 0.5, 95% CI, 0.28 to 0.93) and western (vs central; OR = 0.4, 95% CI, 0.17 to 0.77) parts of Uganda.Conclusion: One in five HCPs reported ACT-failure, mostly verbally to supervisors. The existing ADR-reporting infrastructure should be leveraged to promote the PV of ACT therapeutic ineffectiveness.