Background: Acquired drug resistance remains the greatest clinical hurdle in advanced ovarian cancer suggesting that effective maintenance therapies are lacking. We evaluated cost-effectiveness of available strategies, adjusting for pre-treatment medication costs, infusion center charges, and costs of managing adverse events. Methods: Registration trial data was used to obtain toxicity and median PFS for a) paclitaxel (GOG 212); b) bevacizumab (GOG 218, ICON 7, OCEANS, GOG 213); c) niraparib (NOVA), olaparib (SOLO-2), rucaparib (ARIEL-3); and d) pembrolizumab. Because anti-angiogenesis therapy was studied in different populations, each trial was modeled separately. As phase III randomized trials involving checkpoint inhibition in ovarian cancer are not mature, data for pembrolizumab (available via agnostic indication) were obtained from the phase IB ovarian cohort of KEYNOTE-028. Costs of germline/somatic BRCA testing and those associated with management of neuropathy and immune-mediated adverse events, including endocrinopathies, also factored into the model. Utilizing a Markov chain, patients transitioned through response, hematological and non-hematological complications, progression, and death. Using Medicare data, the costs of infusions and managing toxicities were estimated. Incremental cost-effectiveness ratios (ICER) and quality of adjusted life-months gained were determined for each therapy. Results: Maintenance paclitaxel was most cost-effective at $870/PFS month. Expected costs of PARP inhibitors (PARPi(s)) prior to progression were approx. $471,989 (18.8x paclitaxel, 6.9x pembrolizumab, and 2.2-2.7x bevacizumab). Comparing pembrolizumab to PARPi(s) in BRCA-deficient patients, anti-PD-1 maintenance yielded ICERs per month of life gained of $20,032 (niraparib), $18,444 (rucaparib), and $17,520 (olaparib). Conclusions: Using PFS as the benchmark, high costs of maintenance PARPi(s)/immunotherapy are not mitigated by adjusting for the sequelae that may manifest with maintenance chemotherapy/VEGF inhibition. In terms of economic toxicity, the current trend to study novel combinations is problematic.