A single-photon CMOS image sensor (CIS) design based on pinned photodiode (PPD) with multiple charge transfers and sampling is described. In the proposed pixel architecture, the photogenerated signal is sampled non-destructively multiple times and the results are averaged. Each signal measurement is statistically independent and by averaging, the electronic readout noise is reduced to a level where single photons can be distinguished reliably. A pixel design using this method was simulated in TCAD and several layouts were generated for a 180-nm CMOS image sensor process. Using simulations, the noise performance of the pixel was determined as a function of the number of samples, sense node capacitance, sampling rate and transistor characteristics. The strengths and limitations of the proposed design are discussed in detail, including the trade-off between noise performance and readout rate and the impact of charge transfer inefficiency (CTI). The projected performance of our first prototype device indicates that single-photon imaging is within reach and could enable ground-breaking performances in many scientific and industrial imaging applications.