Systematic experimental studies of KrF laser microdrilling in polymers (PMMA, PET, PS, PC, PI, PEEK) have led to high-aspect-ratio microholes (up to 600) in a final stationary profile. From these results, an original theory is derived, which gives an analytical modeling of the multi-pulse ablation process. In the experiments holes with diameters in the range of 10 to 100 μm and from one to several tens of millimeters in depth, depending on fluence, are obtained for various polymers. The stationary depth increases with fluence and this dependence is well reproduced by the present model. The particular mechanism of radiation propagation and absorption inside the deep laser keyhole is clarified, and does not suggest a significant channeling of the radiation in the forming hole. This mechanism alongside the angular divergence of the beam are important key factors for the mathematical description of high-aspect-ratio laser drilling. As a result (a) the controlling factors of drilling are outlined; (b) final keyhole profile and depth vs. incident fluence are calculated for the rectangular, Gaussian and other spatial distributions of the beam and the comparison with the experiment is given; and (c) the laser drilling is optimized, i.e. the matching conditions for the level and distribution of laser intensity, parameters of the optical focusing scheme and material parameters are derived in an explicit analytical form, allowing us to produce deep keyholes with practically parallel side walls and aspect ratios as high as 300–600.