BACKGROUND: Adherence to radical cure for Plasmodium vivax remains a major challenge for malaria control programmes. Novel regimens, such as 7-day high-dose primaquine regimen and single-dose tafenoquine, may improve treatment adherence and antirelapse effectiveness but can increase the risk of haemolysis in individuals with glucose-6-phosphate dehydrogenase deficiency. Stakeholder (ie, policymakers, providers, patients, etc) perceptions of these risks may significantly influence the acceptability and uptake of these regimens. Understanding these perceptions is essential for policymakers to design effective communication and implementation strategies of novel radical cure strategies. METHODS: Guided by qualitative methodology and a risk perception lens, this study explored P. vivax malaria stakeholders' experiences and interpretations of novel radical cure regimens. Between February and September 2023, 58 semistructured interviews and 6 focus group discussions were conducted at Arba Minch General Hospital and three health centres and health posts within the Gamo Zone of the South Ethiopia Regional State: Lante, Shecha and Shele. Participants included clinical trial staff and participants, health centre personnel, health extension workers and routine care patients. RESULTS: The 7-day-high-dose primaquine regimen and single-dose tafenoquine were viewed as promising solutions to the adherence challenges of the standard 14-day primaquine regimen; however, participants raised concerns about the effectiveness of the shortened treatment duration and the safety of the increased daily dose of primaquine. A risk perception lens revealed that concerns about effectiveness and safety were influenced by prior public health messaging emphasising completion of the full 14-day regimen alongside fears of overdosing and drug-induced haemolysis. Pill characteristics, including number, shape and colour as well as fears of overdosing and drug-induced haemolysis also contributed to apprehension about the safety of these regimens. CONCLUSION: Participants' perceptions of shortened radical cure regimens were shaped by concerns about effectiveness and safety, influenced by prior treatment messaging and pill characteristics such as higher dosing and pill burden. A risk perception lens can inform implementation and communication strategies for novel regimens, where addressing user perceptions alongside practical improvements, such as reducing pill burden, is essential for optimising uptake and adherence.