Background: Autologous stem cell transplantation (ASCT) followed by maintenance therapy is the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma. Maintenance typically consists of lenalidomide (LEN), however, bortezomib (BOR) and bortezomib-lenalidomide combination are other options. The respective toxicity of these regimens has not been well studied. We performed secondary data analysis to compare incidence of serious adverse events associated with each maintenance therapy group during post-ASCT maintenance treatment period. Methods: Data was extracted from the open-access MMRF Researcher Gateway corresponding with interim analysis from the CoMMpass study. We extracted data of first-time autologous stem cell transplant patients who completed maintenance therapy post-ASCT. We categorized patients into three sub groups bortezomib, lenalidomide or combination (bortezomib and lenalidomide) maintenance therapy. Incidence rate for serious adverse events (grade 3 or higher) was calculated by number of events per 100 person-months for each maintenance therapy. Results: 231 patients were eligible for our analysis. 169 patients received lenalidomide, 27 bortezomib and 35 combination. The most common adverse event was neutropenia and second most common is pneumonia. Neutropenia incidence was 1.1,0.7 and 0.9 per 100 person-months in lenalidomide, bortezomib and combination regimens respectively. Incidence of deep vein thrombosis, GI intolerance and peripheral neuropathy 0.1 per 100 person-months respectively was observed in lenalidomide group only. Combination maintenance had the highest total adverse event incidence rate of 5.4 per 100 person-months. Incidence of 1.7 and 3.8 per 100 person-months is observed in bortezomib and lenalidomide cohorts respectively. Conclusions: Lenalidomide and bortezomib maintenance had similar incidence of serious adverse events. A higher incidence of serious adverse events was noted in the combination lenalidomide/bortezomib regimens. Interestingly, we observed lower incidence of adverse events in all groups in CoMMpass study compared to respective clinical trials involving maintenance regimens. This may be due to under reporting of adverse events in CoMMpass study. The incidence of adverse events mentioned above should be interpreted in the context of drugs and other factors involved in the disease.