To study the efficacy and safety of single large volume leukapheresis by using generic G-CSF or G-CSF plus Plerixafor in achieving adequate stem cell yield and various factors influencing thereof in newly diagnosed multiple myeloma patients undergoing autologous stem cell transplant . This prospective study was undertaken among 55 newly diagnosed multiple myeloma patients undergoing autologous stem cell transplant and aged between 18 and 75 years. Mobilization and harvesting of stem cells were performed by using GCSF or GCSF plus Plerixafor and large volume leukapheresis, respectively. A stem cell yield of ≥2 × 10⁶ kg^–1 and the number of apheresis procedures were primary efficacy endpoints, while the ideal stem cells yield >5 × 10⁶ kg^–1, the engraftment day and D100 response/graft sustainability were secondary endpoints. The primary endpoint was achieved in all cases in both the groups by using a single LVL leukapheresis procedure. Fulfillment of all the secondary endpoints was satisfactory and comparable in both the groups. Age, pre-apheresis CD34+ count and number of interruptions during the LVL were significant factors influencing the stem cell yield (p < 0.05). Adverse drug reactions during the apheresis and post-ASCT period were manageable. The LVL is safe and cost-effective in attaining a minimum of CD34+ cells in a single procedure with manageable adverse reactions. Judicious intervention during the procedure may be helpful in ensuring the adequate yield.