A reversed-phase high-performance thin-layer chromatographic method combined with image analysis was developed and validated for simultaneous quantitative evaluation of paracetamol and caffeine in pharmaceutical preparations. RP-HPTLC-W18 chromatographic plates were used as the stationary phase and methanol:glacial acetic acid:water (25:4.3:70.7; v:v:v) as the mobile phase. The detection of the spots and the image documentation were carried out under 254 nm UV radiation. Quantitative evaluation of the studied compounds was performed by Sorbfil TLC software. The proposed analytical method was characterized by good linearity, sustained by the correlation coefficient of 0.9974 for paracetamol and 0.9982 for caffeine. Limit of detection and limit of quantitation were found to be 0.100 and 0.191 μg spot−1, for paracetamol, as well as 0.040 and 0.076 μg spot−1, for caffeine. The results of the recovery studies are in the range of 99.56–106.84% and the repeatability of the method was shown to be excellent (RSD < 1.88%).