Optimal collections of mobilized CD34+ cells are important in terms of both patient toxicity and cost. The factors that determine CD34+ collection efficiency (CD34eff) of cell separators have not been well studied. In addition, because several cell separators are available, the type of collection device may also be a significant variable. Previous studies comparing the Baxter-Fenwal CS3000 and the COBE Spectra have not yielded consistent conclusions. Therefore, we retrospectively analyzed the collection outcomes of 163 consecutive donors with a peripheral CD34+ cell concentration (pCD34) of > or =5 cells/microl on the first collection that had been harvested on one or the other device. The CS3000 was found to yield a significantly higher CD34eff (50% vs. 39%, P = 0.006). However, donors were not balanced for several prognostic factors, which may contribute to CD34eff including mobilization with G-CSF vs. chemotherapy+G-CSF, average flow rate, and total volume of peripheral blood processed. When appropriate variables were included in a stepwise multiple variable analysis, cell separator type emerged as a significant independent predictive factor for CD34eff (P = 0.018). Our data indicates that the CS3000 will, on average, show a higher absolute CDeff of 8%. Furthermore, since the two devices differ in mechanism, prognostic factors may also differ. Comparisons suggest that peripheral blood WBC and hematocrit may be more important predictors for the CS3000.