Purpose: We compared methods to control bias and confounding in observational studies including inverse probability weighting (IPW) and stabilized IPW (sIPW). These methods often require iteration and post-calibration to achieve covariate balance. In comparison, entropy balance (EB) optimizes covariate balance a priori by calibrating weights using the target's moments as constraints., Methods: We measured covariate balance empirically and by simulation by using absolute standardized mean difference (ASMD), absolute bias (AB), and root mean square error (RMSE), investigating two scenarios: the size of the observed (exposed) cohort exceeds the target (unexposed) cohort and vice versa. The empirical application weighted a commercial health plan cohort to a nationally representative National Health and Nutrition Examination Survey target on the same covariates and compared average total health care cost estimates across methods., Results: Entropy balance alone achieved balance (ASMD ≤ 0.10) on all covariates in simulation and empirically. In simulation scenario I, EB achieved the lowest AB and RMSE (13.64, 31.19) compared with IPW (263.05, 263.99) and sIPW (319.91, 320.71). In scenario II, EB outperformed IPW and sIPW with smaller AB and RMSE. In scenarios I and II, EB achieved the lowest mean estimate difference from the simulated population outcome ($490.05, $487.62) compared with IPW and sIPW, respectively. Empirically, only EB differed from the unweighted mean cost indicating IPW, and sIPW weighting was ineffective., Conclusion: Entropy balance demonstrated the bias-variance tradeoff achieving higher estimate accuracy, yet lower estimate precision, compared with IPW methods. EB weighting required no post-processing and effectively mitigated observed bias and confounding. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)