Introduction: Plasmodium vivax is a major cause of recurrent malaria in Papua, Indonesia, because dormant liver hypnozoites can trigger relapses. Adherence to radical cure with 3-day dihydroartemisinin–piperaquine (DHP) plus 14-day primaquine is essential for relapse prevention but is often hindered by sociocultural factors, risk perception, and treatment duration. This study evaluated a culturally tailored adherence-support intervention centred on an adherence card developed from a Papuan emic perspective to improve adherence among patients with P. vivax malaria. Methods: A cluster-randomised controlled trial was conducted in six primary health centres in Jayapura City (three intervention clusters and three control clusters) from February to June 2025. A total of 278 participants were recruited from the randomised PHC clusters; 137 participants were in the intervention clusters and received the culturally tailored adherence-support intervention, including the adherence card, education, medication monitoring, and cadre follow-up, while 141 participants in the control clusters received standard malaria services. Adherence was assessed using pill count and self-report, with intention-to-treat (ITT) as the primary analysis. Intervention effects were expressed as cluster-adjusted risk ratios (RRs), and factors associated with 14-day primaquine adherence were explored using cluster-adjusted regression analysis. Results: In the intention-to-treat analysis, full adherence to the complete DHP and 14-day primaquine regimen, confirmed by pill count and self-report, was higher in the intervention group than in the control group (85.0% vs 44.4%; RR = 1.91; 95% CI: 1.07–3.41; p = 0.039). In the exploratory cluster-adjusted analysis of 14-day primaquine adherence, study arm was the only factor significantly associated with adherence after adjustment (aOR = 7.04; 95% CI: 1.41–35.18; p = 0.028). Conclusion: The culturally tailored adherence-support intervention improved full adherence to the DHP and 14-day primaquine regimen among patients with P. vivax malaria in the participating PHCs in Jayapura. The findings support further evaluation of this intervention in other settings.