A flow injection post chemiluminescence (FI-PCL) reaction was found when astemizole was mixed with the CL reaction mixture of N-bromosuccinimide and calcein under alkaline conditions. Based on this observation, a simple and sensitive post chemiluminescence (PCL) technique for the assay of astemizole was described. Under the optimized conditions, the PCL values responded linearly to the concentration of astemizole in the range 1.0 × 10−3–3.0 µg/mL, with a detection limit of 7.0 × 10−4 µg/mL. The relative standard deviation was 1.7% for 1.0 × 10−2 µg/mL astemizole solution (n = 13). It was applied to the determination of astemizole in pharmaceutical preparations with satisfactory results.