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This paper presents a time-resolved CMOS image sensor with draining-only modulation (DOM) pixels, for time-domain fluorescence lifetime imaging. In the DOM pixels using a pinned photodiode (PPD) technology, a time-windowed signal charge transfer from a PPD to a pinned storage diode (PSD) is controlled by a draining gate only, without a transfer gate between the two diodes. This structure allows a potential barrierless and trapless charge transfer from the PPD to the PSD. A 256 × 256 pixel time-resolved CMOS imager with 7.5 × 7.5 μm2 DOM pixels has been implemented using 0.18-μm CMOS image sensor process technology with PPD option. The prototype demonstrates high sensitivity for weak signal of less than one electron per light pulse and accurate measurement of fluorescence decay process with subnanosecond time resolution.