Financial burden on households due to health care is high in Nepal. High health care expenditure stands as a major obstacle in achieving universal health coverage, an explicit target of sustainable development goals. This study investigated the factors affecting health care expenditure in the first piloted government health insurance program in Kailali district of Nepal. A cross-sectional survey was conducted from January to February 2018 among 1048 households (6480 individuals) located in 26 wards of Kailali district after 21 months of the implementation of health insurance program in Nepal. The sample was selected in two stages, first stage being the selection of wards and second being the households. The analysis was restricted to only those individuals who reported illness and health care expenditure in the month prior to the survey. The data were analyzed using Mann Whitney U test, Krusakal Wallis test, and log-linear regression model. Out of 1439 ill individuals who reported health expenditure in the month prior to survey, the monthly average expenditure was 4907 Nepalese Rupees (NPR) (43.54 USD)- the medical cost was the main driver of health care expenditure. The log-linear multiple regression analysis revealed that health care expenditure was significantly associated with economic well-being, enrolment in health insurance, household size, type of residence, access to health facility, type of illness experienced, and severity of illness. The health insurance coverage was found to have reduced health care expenditure and it was progressive with the rich spent more on health care. Since health insurance coverage was associated with lower expenditure, findings from this study could inform policy in the on-going national health insurance debate in Nepal. The government health insurance program of Nepal is currently at initial stage, and if implemented effectively, will help financially vulnerable groups by covering health care expenditure.