Mass spectrometers have an enormous number of user-changeable parameters that drastically affect the observed mass spectrum. Using optimal parameters can significantly improve mass spectrometric data by increasing signal stability and signal-to-noise ratio, which decreases the limit of detection, thus revealing previously unobservable species. However, ascertaining optimal parameters is time-consuming, tedious, and made further challenging by the fact that parameters can act dependently on each other. Consequently, suboptimal parameters are frequently used during characterization, reducing the quality of results. OptiMS, an open-source, cross-platform program, was developed to simplify, accelerate, and more accurately determine optimal mass spectrometer parameters for a given system. It addresses common difficulties associated with existing software such as slow performance, high costs, and limited functionality. OptiMS efficacy was demonstrated through its application to multiple systems, quickly and successfully optimizing instrument parameters unassisted to maximize a user-defined metric, such as the intensity of a particular analyte. Additionally, among other features, OptiMS allows running of a sequence of predefined parameter configurations, reducing the workload of users wishing to obtain mass spectra under multiple sets of conditions.