Rapid assessment of laser-induced photochemistry in single microdroplets is afforded by on-demand microdroplet generation coupled to a commercial ion-trap mass spectrometer. Single microdroplets (diameter 50 μm, 65 pL) fall on a steel needle held at +2 kV where they subsequently form a spray that is directed toward the inlet of an ion-trap mass spectrometer. It is demonstrated that single microdroplet mass spectra are recordable, one at a time, for methanol droplets containing 100 μM 4-iodoaniline. Extending on this, to probe laser-initiated photochemistry in single picoliter volumes, a UV laser pulse is timed to intercept the droplet before hitting the needle. Comparison of laser-on and laser-off mass spectra reveals the laser-initiated photochemical products. We demonstrate the technique by following UV laser initiated chemistry in methanol droplets containing 4-iodoaniline and 3-(iodomethyl)-N,N,N-trimethylbenzenamine and reveal numerous products within a few hundred single droplet experiments over several minutes. This technique allows for rapid detection of laser-initiated photochemistry in single picoliter volumes.