A small number of informative biallelic single nucleotide polymorphisms (SNPs) have been proposed to be an economical method to fast-track the genotyping and relatedness analysis of Plasmodium falciparum in malaria-endemic areas. Whilst used successfully in low-transmission areas where infections are monoclonal and highly related,  we present the first study to evaluate the performance of these 24- and 96-SNP molecular barcodes in African countries characterised by moderate-to-high transmission. Using haplotypes generated from the MalariaGEN P. falciparum Community Project version 6 database, 52.3% of infections were multiclonal, generating high frequencies of mixed-allele calls (MACs) per isolate. Both multiclonality and low heterozygosity of SNPs impeded haplotype construction for analyses of relatedness. Although fewer SNPs provided usable data, these SNP barcodes weakly identified genetic differentiation across large geographic distances. However, both minor and major alleles' frequencies were temporally unstable. We conclude that these standardised SNP barcodes are vulnerable to ascertainment bias. While large numbers of SNPs acquired by whole-genome sequencing and computational methods to construct haplotypes present a way forward, these approaches may not be practical or cost-effective for surveillance on large scales in malaria-endemic areas.