OBJECTIVES: Decision-analytic cost-effectiveness (CE) models combine many different parameters, which are often obtained after indirect meta-analysis. The choice of method may affect CE estimates. We aimed to compare different methods of indirect meta-analysis, especially with respect to health economic (HE) outcomes as the costs per QALY. METHODS: A reference patient population (N=50,000) was simulated, from which sets of trials were drawn, comparing two of four fictitious interventions. Heterogeneity was added in pre-specidifed scenarios by drawing from subpopulations. Trial-specific parameter estimates were combined using Bucher’s direct and indirect comparisons, and the mixed treatment comparison (MTC) methods by Song, Puhan and Lu/Ades (fixed and random effects). Pooled parameters were entered into a HE Markov model. We studied whether differences were systematic by repeating the sampling and indirect meta-analysis 1,000 times. Estimated parameters and HE outcomes were compared using coverage, bias, mean absolute deviation (MAD) and statistical power. RESULTS: Bucher’s methods are outperformed by the MTC methods, generally overestimating uncertainty and having a relatively large MAD. HE outcomes for Song have low MAD and bias, but uncertainty is overestimated. Puhan’s method does not overestimate uncertainty and generally is the closest to the true parameter value, regardless of heterogeneity. Both lead to the least amount of uncertainty reflected in the CE acceptability curve (CEAC). Lu/Ades fixed effects performs slightly worse than Puhan and Song in terms of bias and MAD. Uncertainty is generally overestimated, regardless of heterogeneity. It is also slightly less certain in the CEAC. Only with considerable heterogeneity does the Lu/Ades random effects model have the lowest bias. It still shows large MAD and uncertainty is almost always overestimated. CONCLUSIONS: Regardless of heterogeneity, combining direct and indirect evidence improves results. HE outcomes produced with Puhan's method have the best statistical properties.