The collection of PBSC for transplantation requires repetitive leukapheresis, typically via central venous catheters (CVC). To assess the complications of this procedure, we reviewed 75 consecutive PBSC transplant candidates requiring 554 leukapheresis on a Haemonetics V50 Plus apheresis system. CVC occlusion necessitating thrombolytic therapy or cancellation of the procedure was the most commonly observed complication, occurring among 37 patients on 86 occasions (15.9% of CVC-aided collections). Thrombolytic therapy was successful in 85%. Of the patients, 16% experienced an infectious complication during the PBSC harvesting; chemotherapy mobilization significantly increased this risk, whereas growth factor mobilization was protective (p < 0.02). Hematologic complications including anemia (median postapheresis nadir hemoglobin 8.8 g/dl) and transient thrombocytopenia (median postapheresis nadir 64,000/microliters) required transfusional support among 30.7% and 14.7% of patients, respectively. The use of chemotherapy mobilization was correlated with increased need for support of both red cells and platelets (p < 0.001). Additional complications included catheter placement problems, symptomatic citrate-related hypocalcemia, transient hypotension, and machine-related malfunctions. Although the complications of the PBSC harvests were manageable, given their frequency the decision to pursue this form of hematopoietic rescue in preference to traditional operative bone marrow harvesting must address these risks.