BackgroundCOVID-19 was first identified in December 2019 in the city of Wuhan, China. The virus quickly spread and was declared a pandemic on March 11, 2020. After infection, symptoms such as fever, a (dry) cough, nasal congestion, and fatigue can develop. In some cases, the virus causes severe complications such as pneumonia and dyspnea and could result in death. The virus also spread rapidly in the Netherlands, a small and densely populated country with an aging population. Health care in the Netherlands is of a high standard, but there were nevertheless problems with hospital capacity, such as the number of available beds and staff. There were also regions and municipalities that were hit harder than others. In the Netherlands, there are important data sources available for daily COVID-19 numbers and information about municipalities. ObjectiveWe aimed to predict the cumulative number of confirmed COVID-19 infections per 10,000 inhabitants per municipality in the Netherlands, using a data set with the properties of 355 municipalities in the Netherlands and advanced modeling techniques. MethodsWe collected relevant static data per municipality from data sources that were available in the Dutch public domain and merged these data with the dynamic daily number of infections from January 1, 2020, to May 9, 2021, resulting in a data set with 355 municipalities in the Netherlands and variables grouped into 20 topics. The modeling techniques random forest and multiple fractional polynomials were used to construct a prediction model for predicting the cumulative number of confirmed COVID-19 infections per 10,000 inhabitants per municipality in the Netherlands. ResultsThe final prediction model had an R2 of 0.63. Important properties for predicting the cumulative number of confirmed COVID-19 infections per 10,000 inhabitants in a municipality in the Netherlands were exposure to particulate matter with diameters <10 μm (PM10) in the air, the percentage of Labour party voters, and the number of children in a ...