Background: Malaria diagnosis relies mainly on the use of rapid diagnostic tests (RDTs). The majority of commercial RDTs used in Africa detect the Plasmodium falciparum histidine-rich protein 2 (PfHRP2). pfhrp2/3 gene deletions can therefore lead to false-negative RDT results. This study aimed to evaluate the frequency of PCR-confirmed, false-negative P. falciparum RDT results in Monrovia, Liberia.Methods: We used PfHRP2-based RDT (Paracheck Pf®) and microscopy results from 1038 individuals with fever or history of fever (n=951) and pregnant women at first antenatal care (ANC) visit (n=87) enrolled in the Saint Joseph Catholic Hospital (Monrovia) from March to July 2019 to assess the frequency of false-negative RDT results. True false negatives were confirmed by detecting the presence of P. falciparum DNA by quantitative PCR in samples from individuals with discrepant RDT and microscopy resultsResults: One hundred and eighty-six (19.6%) and 200 (21.0%) of the 951 febrile participants had a P. falciparum positive result by RDT and microscopy, respectively. Positivity rate increased with age and the reporting of joint pain, chills and shivers, vomiting and weakness, and increased with the presence of coughs and nausea. The positivity rate at first ANC visit was 5.7% (n=5) and 8% (n=7) by RDT and microscopy, respectively. Out of 207 Plasmodium infections detected by microscopy, 22 (11%) were negative by RDT. qPCR confirmed absence of P. falciparum DNA in the sixteen RDT-negative but microscopy-positive samples which were available for molecular testing. Conclusion: There is no qPCR-confirmed evidence of false-negative RDT results due to pfhrp2/pfhrp3 deletions in this study conducted in Monrovia (Liberia). This indicates the appropriate performance of PfHRP2-based RDTs for the diagnosis of malaria in Liberia. Nevertheless, active surveillance for the emergence of PfHRP2 deletions is required.