A method for both qualitative screening and quantitative determination of 569 pesticides in honeysuckle was developed based on ultrahigh-performance liquid chromatography (UHPLC) coupled to quadrupole-Orbitrap high resolution mass spectrometry and an in-house executable compound database involving the theoretical masses of precursor and fragment ions and retention times. Different workflows were evaluated, validated and compared including Full MS-SIM, Full MS/ddMS2, Full MS/AIF and Full MS/DIA. For qualitative analysis, Full MS/DIA showed relatively low screening detection limits (SDLs) for most pesticides, but its MS2 identification seemed to be not reliable enough. Full MS/ddMS2 showed good repeatability of fragment ion recognition and less false positives. For quantitative analysis, the results of four workflows were comparable in terms of linearity and trueness, while Full MS-SIM and Full MS/ddMS2 gave better precision than the other two workflows for most pesticides at the spiking level of 0.01 mg/kg. Therefore, UHPLC-Full MS/ddMS2 was considered as the optimal workflow for both qualitative and quantitative analysis of honeysuckle samples. Pesticides were present in 75 of the 82 investigated samples, with concentrations ranging from 10.0 to 4116.9 μg/kg in some of the most severely contaminated samples. Copyright © 2019. Published by Elsevier B.V.