CTFFIND4 is an updated version of the widely used program CTFFIND3 for estimating objective lens defocus and astigmatism parameters from transmission electron micrographs. The new version is significantly faster and more suitable for modern technologies such as dose fractionation and phase plates. It preserves the accuracy of the original algorithm while allowing for higher throughput. The algorithm models the microscope's contrast transfer function (CTF) as a 2-dimensional function of the spatial frequency vector and estimates the parameters by fitting this model to the image's amplitude spectrum. The program includes a scoring function that maximizes the similarity between the theoretical CTF and the experimental spectrum, with an option to penalize astigmatic CTFs. CTFFIND4 also provides diagnostic images and 1D profiles to assess the quality of the fit, and can process dose-fractionated movies and micrographs recorded using phase plates. Benchmarking tests show that CTFFIND4 is about 10 times faster than CTFFIND3 and provides similar accuracy in defocus parameter estimation. The program outputs a summary text file with final estimates and diagnostic plots to help users evaluate the quality of the fit.CTFFIND4 is an updated version of the widely used program CTFFIND3 for estimating objective lens defocus and astigmatism parameters from transmission electron micrographs. The new version is significantly faster and more suitable for modern technologies such as dose fractionation and phase plates. It preserves the accuracy of the original algorithm while allowing for higher throughput. The algorithm models the microscope's contrast transfer function (CTF) as a 2-dimensional function of the spatial frequency vector and estimates the parameters by fitting this model to the image's amplitude spectrum. The program includes a scoring function that maximizes the similarity between the theoretical CTF and the experimental spectrum, with an option to penalize astigmatic CTFs. CTFFIND4 also provides diagnostic images and 1D profiles to assess the quality of the fit, and can process dose-fractionated movies and micrographs recorded using phase plates. Benchmarking tests show that CTFFIND4 is about 10 times faster than CTFFIND3 and provides similar accuracy in defocus parameter estimation. The program outputs a summary text file with final estimates and diagnostic plots to help users evaluate the quality of the fit.