BACKGROUND: Malaria is a preventable disease that causes huge morbidity and mortality in malaria-endemic areas, especially among children and pregnant women. The malaria control programme focuses on the prevention of mosquito bites using insecticide-treated nets (ITNs) and mosquito aerosol sprays and coils, as well as prevention of severe disease among those infected through prompt and adequate treatment. The success of the malaria control programme in Ghana is dependent on the malaria prevention practices of people in the community. Therefore, this study evaluated the malaria prevention practices of participants in four districts of the Volta Region of Ghana. METHODS: This was a cross-sectional study conducted in Ketu South, Nkwanta South, Hohoe Municipality and Ho West districts of the Volta Region of Ghana. Questionnaire were administered to adults who consented to each household visited. Questions were asked on the socio-demographics and malaria prevention practices of the households. Data analysis was done using SPSS version 23 with frequency distribution done for all the variables. Pearson chi-square was used to determine the significant association between socio-demographics and malaria prevention practices, and Multivariate nominal logistic regression analysis was used to model the relationship between dichotomous dependent variables (ITN ownership and usage) and independent variables. RESULTS: Out of the 2493 participants; 2234 (89.6%) owned ITN and 1528 (68.4%) used ITN a night before this study, 768 (30.8%) used mosquito aerosol spray and 368 (15%) used mosquito coil. More females significantly owned ITN than males (1293, 92.4%, p ≤ 0.001). Participants from Ketu South had 1.5 times higher odds of owning an ITN compared to Ho West whose odds are not different from Nkwanta South or Hohoe (AOR, 1.56 [95% 1.09-2.22]; p = 0.01). In terms of ITN usage, participants in Nkwanta South were less likely to use ITN compared to the other districts; AOR, 0.434 [95% CI 0.31-0.62, p < 0.001]. Also, of the 668 participants that had a fever within the past 3 days, 268 (40.1%) visited a patent medicine store and 156 (23.4%) visited health facilities. CONCLUSION: There is high ownership of ITNs, but relatively low utilization among the community members. Education on malaria prevention practices should be intensified and continuous among the population of the Volta Region to ensure the success of malaria control in the region.