Background. Despite significant progress achieved globally in reducing malaria burden, still it is one of the major public health and economic problems in Ethiopia. Investigation of the local genetic polymorphism of P. falciparum, the most virulent and predominant malaria parasite primarily targeted in malaria control and elimination program, is paramount to assess intensity of parasite transmission. Analysis of the block 3 region of the msp-2 gene of P. falciparum provides strong molecular evidence to evaluate the real picture of malaria epidemiology to fine-tune the ongoing control and elimination programs in the region. Thus, this study was aimed at examining the status of such polymorphic gene and its implications in Adama and its surroundings. Methods. 148 isolates from patients with uncomplicated falciparum malaria were collected in the study from September 2019 to August 2020. Tween® 20 and the Chelex method were employed for parasite DNA extraction. msp-2 allelic families were genotyped by using nested polymerase chain reaction targeting its 3D7 and FC27 allelic variants followed by gel electrophoresis for fragment analysis. Results. Seventeen different polymorphic forms of msp-2 allelic fragments were detected in the study area. Moreover, 47 (31.8%) and 41(27.7%) were detected for 3D7 and FC27 allelic families, respectively. Furthermore, the multiclonal allele type accounted for 60 (40.5%). The mean MOI was 1.4, and the heterogeneity index (He) is 0.49 indicating nearly intermediate malaria transmission in the study area. Conclusions. The study revealed nearly intermediate genetic diversity and mean MOI of P. falciparum in the study area, demanding further scale up of the ongoing control and elimination efforts.