Caffeine-H3PO4 along with caffeine-HClO4 and caffeine-HNO3 have been prepared and applied for one-pot preparation of bis(indolyl) methanes, 4,4′-(arylmethylene) bis(1H-pyrazol-5-ols), 3,3′-(arylmethylene) bis(4-hydroxycoumarins), 2,4,5-trisubstituted imidazoles, 1‐amidoalkyl‐2‐naphthols, and polyhydroquinolines. The catalysts were characterized using Fourier-transform infrared (FTIR) spectroscopy, 1H and 13C nuclear magnetic resonance (NMR), powder X-ray diffraction (PXRD) analysis, thermogravimetric analysis (TGA), and liquid chromatography (LC)–mass spectroscopy (MS) techniques. The results indicated high product yield, short reaction time, facile separation of catalyst, and easy work-up procedure, suggesting that caffeine-H3PO4 can be considered to be an efficient acidic catalyst for organic transformations.