A sub-nanosecond visible laser coupled with a liquid chromatograph is utilized for atmospheric pressure laser ionization (APLI). We reveal that the range of applicable substances for nonresonant three-photon ionization is determined by the proton affinity and the ionization potential, the latter of which is lowered by solvation with eluents. APLI with a visible laser can be used for fragmentation-and background-free detection of analytes as well as to investigate the ionization threshold of solvated molecules.