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Background: Since 2006, Nepal has experienced frequent Dengue fever (DF) outbreaks. Up to now, there have been no knowledge, attitude and practice (KAP) studies carried out on DF in Nepal that have included qualitative in-depth and quantitative data. Thus, we aimed to explore and compare the KAP of people residing in the lowland (< 1500 m) and highland (> 1500 m) areas of Nepal.Methods: A cross-sectional mixed-method study was conducted in six districts of central Nepal in September-October 2018 including both quantitative (660 household surveys) and qualitative data (12 focus group discussions and 27 in-depth interviews). The KAP assessment was executed using a scoring system and defined as high or low based on 80% cut-off point. Logistic regression was used to investigate the associated factors, in quantitative analysis. The deductive followed by inductive approach was adopted to identify the themes in the qualitative data.Results: The study revealed that both the awareness about DF and prevention measures were low. Among the surveyed participants, 40.6% had previously heard about DF with a significantly higher number in the lowland areas. Similarly, IDI and FGD participants from the lowland areas were aware about DF, and it's associated symptoms, hence they were adopting better preventive practices against DF. The findings of both the qualitative and quantitative data indicate that people residing in the lowland areas had better knowledge on DF compared to people in highland areas. All IDI participants perceived a higher chance of increasing future dengue outbreaks due to increasing temperature and the mobility of infected people from endemic to non-endemic areas. The most quoted sources of information were the television (71.8%) and radio (51.5%). Overall, only 2.3% of the HHS participants obtained high knowledge scores, 74.1% obtained high attitude scores and 21.2% obtained high preventive practice scores on DF. Among the socio-demographic variables, the area of residence, educational level, age, monthly income, SES and occupation were independent predictors of knowledge level, while the education level of the participants was an independent predictor of the attitude level.Conclusions: Our study found a very low level of knowledge and insufficient preventive practices. This highlights an urgent need for extensive dengue prevention programs in both highland and lowland communities of Nepal. [ABSTRACT FROM AUTHOR]