Plerixafor augments PBSC collection, but the optimal approach for incorporating it into mobilization is uncertain. Forty-nine consecutive patients mobilized with G-CSF alone were analyzed, and a day 4 peripheral blood CD34(+) cell count of 0.015/ml was found to predict for a day 5 apheresis yield of 2 × 10(6) CD34(+) progenitors/kg, our institutional minimum necessary for a single autologous transplant. On the basis of this relationship, a clinical guideline was developed which recommended pre-emptive use of plerixafor if the day 4 peripheral blood CD34(+) cell count was between 0.005 and 0.015/ml. A total of 166 consecutive subjects with lymphoma or plasma cell dyscrasias underwent G-CSF mobilization after adoption of this care pathway, and the mobilization failure rate was only 7% in patients managed per guideline. The median PBSC yield was 6.3 × 10(6) CD34(+) progenitors/kg with G-CSF (day 4 peripheral blood CD34(+) cell > 0.015/ml) and 4.9 × 10(6) CD34(+) progenitors/kg with G-CSF+plerixafor (day 4 peripheral blood CD34(+) cell 0.005-0.015/ml). The median number of days of apheresis was 2 in both groups. This clinical guideline is an effective mobilization algorithm that minimizes mobilization failures, reduces poor apheresis yields, does not require risk factor identification and is simple to implement.