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Background: Outside of Africa, P. falciparum and P. vivax usually coexist. In such co-endemic regions, successful malaria control programs have a greater impact on reducing falciparum malaria, resulting in P. vivax becoming the predominant species of infection. Adding to the challenges of elimination, the dormant liver stage complicates efforts to monitor the impact of ongoing interventions against P. vivax. We investigated molecular approaches to inform the respective transmission dynamics of P. falciparum and P. vivax and how these could help to prioritize public health interventions. Methodology/ Principal Findings: Genotype data generated at 8 and 9 microsatellite loci were analysed in 168 P. falciparum and 166 P. vivax isolates, respectively, from four co-endemic sites in Indonesia (Bangka, Kalimantan, Sumba and West Timor). Measures of diversity, linkage disequilibrium (LD) and population structure were used to gauge the transmission dynamics of each species in each setting. Marked differences were observed in the diversity and population structure of P. vivax versus P. falciparum. In Bangka, Kalimantan and Timor, P. falciparum diversity was low, and LD patterns were consistent with unstable, epidemic transmission, amenable to targeted intervention. In contrast, P. vivax diversity was higher and transmission appeared more stable. Population differentiation was lower in P. vivax versus P. falciparum, suggesting that the hypnozoite reservoir might play an important role in sustaining local transmission and facilitating the spread of P. vivax infections in different endemic settings. P. vivax polyclonality varied with local endemicity, demonstrating potential utility in informing on transmission intensity in this species. Conclusions/ Significance: Molecular approaches can provide important information on malaria transmission that is not readily available from traditional epidemiological measures. Elucidation of the transmission dynamics circulating in a given setting will have a major role in prioritising malaria control strategies, particularly against the relatively neglected non-falciparum species. Author Summary: The malaria parasite Plasmodium vivax is a growing public health burden across the globe. Largely overshadowed by the more fatal P. falciparum parasite, increasing reports of anti-malarial drug resistance and life-threatening disease complications demand concerted efforts to eliminate P. vivax. Outside of Africa, P. vivax usually co-exists with P. falciparum. In these regions, malaria interventions have demonstrated greater success against falciparum. The authors genotyped P. vivax and P. falciparum parasites from 4 co-endemic sites in Indonesia, and used the data to gauge how frequently and how focally parasites were transmitted, and how much they spread between sites. Their results indicated that whilst the P. falciparum populations displayed evidence of low and unstable transmission, the P. vivax populations were more diverse and exhibited more stable transmission patterns, requiring different intervention approaches. Relative to P. falciparum, the P. vivax parasites demonstrated evidence of greater spread between populations, possibly facilitated by the dormant liver stage which enables P. vivax to be carried asymptomatically in patients for long periods of time. These findings highlight the need to reconcile the intervention requirements for non-falciparum malaria species in co-endemic regions, and the general utility of parasite genotyping to facilitate surveillance. [ABSTRACT FROM AUTHOR]