To compare the real-world effectiveness and safety of monotherapy nab-paclitaxel and paclitaxel in patients with platinum-resistant ovarian cancer (PROC). COMPASS is a retrospective, observational study using deidentified patient data from the longitudinal US Flatiron Health Research Database in patients with PROC who received monotherapy nab-paclitaxel or paclitaxel. Real-world progression-free survival (rwPFS), overall survival (OS), and prespecified real-world adverse events (rwAEs) were assessed. Cohorts were weighted by the inverse probability of treatment (IPTW) approach. Of the 225 patients included, 67 received nab-paclitaxel and 158 received paclitaxel monotherapy. Most patients were > 65 years old with an Eastern Cooperative Oncology Group performance status of 0-1 and were treated in the community setting. rwPFS and OS were comparable across cohorts (rwPFS: unadjusted hazard ratio [HR],1.11; 95 % CI, 0.82-1.49; IPTW-adjusted HR, 1.03; 95 % CI, 0.66-1.63; OS: unadjusted HR, 0.95; 95 % CI, 0.69-1.3; IPTW-adjusted HR, 1.11; 95 % CI, 0.79-1.56). A sensitivity analysis using doubly robust IPTW showed consistent results. Incidence rates of anemia, diarrhea, fatigue, infusion-related reactions, nausea/vomiting, peripheral neuropathy, and thrombocytopenia were lower with nab-paclitaxel than with paclitaxel, while those of neutropenia, febrile neutropenia, and leukopenia were higher. The frequency of peripheral neuropathy in the nab-paclitaxel cohort (14 %) was half that of the paclitaxel cohort (28 %). The observed trends in rwAEs persisted when adjusted for duration of exposure. Nab-paclitaxel demonstrated comparable effectiveness to paclitaxel with a lower rate of peripheral neuropathy, suggesting that nab-paclitaxel is an effective treatment option and a relevant comparator for clinical trials of patients with PROC.