A 1 mm(3) resolution clinical positron emission tomography (PET) system employing 4608 position-sensitive avalanche photodiodes (PSAPDs) is under development. This paper describes a detector multiplexing technique that simplifies the readout electronics and reduces the density of the circuit board design. The multiplexing scheme was validated using a simulation framework that models the PSAPDs and front-end multiplexing circuits to predict the signal-to-noise ratio and flood histogram performance. Two independent experimental setups measured the energy resolution, time resolution, crystal identification ability and count rate both with and without multiplexing. With multiplexing, there was no significant degradation in energy resolution, time resolution and count rate. There was a relative 6.9 ± 1.0% and 9.4 ± 1.0% degradation in the figure of merit that characterizes the crystal identification ability observed in the measured and simulated ceramic-mounted PSAPD module flood histograms, respectively.