Ion mobility helps resolve complex proteomics samples, but data structures can be unwieldy and lead to long post-acquisition analysis times. We adapted the fast search engine MSFragger for timsTOF data, and developed IonQuant for accurate quantification. These tools are part of a complete pipeline that is well suited for the analysis of timsTOF in terms of identification sensitivity, quantification accuracy, and runtimes. We additionally demonstrate complex analyses, including semi-enzymatic database search to monitor gas-phase fragmentation in early timsTOF data.