The anomeric free energy difference between the alpha (axial) and beta (equatorial) anomers of D-mannose was calculated using standard free energy methods (free energy perturbation (FEP) and potential of mean force (PMF)) and with the recently described MC(JBW)/SD simulation technique. The final results obtained with our new united atom AMBER* force field and GB/SA continuum water are FEP 0.28 +/- 0.10, PMF 0.20 +/- 0.10, MC(JBW)/SD, and 0.25 +/- 0.02 kcal/mol in favor of the alpha anomer, all in good agreement with the experimental value (0.34-0.45 kcal/mol). Convergence, as measured by the stability of the results and the standard deviations, is reached at least an order of magnitude faster with MC(JBW)/SD than with the other two methods.