Out-of-pocket expenses in healthcare show the level of direct payments by individuals paying for the healthcare services that are not covered by the insurance. In the Republic of Serbia, high level of out-of-pocket expenses is present considering dominant Bismarck model of healthcare system and level of user income. Previous research shows the significant impact of the socio-economic and healthcare system indicators afecting out-of-pocket expenses. The objective is to perform a cross-sectional analysis of the economic, healthcare, and demographic variables impact on the out-of-pocket expenses. We use quantitative methods of analysis of data collected for the data time frame from 20002018. Results show a high impact of the 7 out of 13 factors we explored.