Background: Adjusted indirect comparison (AIC) has been increasingly used in health technology assessment because of a lack of trial data from direct head-to-head comparisons. Objective: To conduct an updated methodology review on the validity of adjusted indirect comparison. Methods: We searched MEDLINE to identify meta-analyses of RCTs that provided sufficient data to compare the results of direct and indirect comparisons. Risk of bias was assessed in terms of completeness of literature search, assessment of trial similarity and evidence consistency. The discrepancy between the direct estimate and AIC estimate is calculated as the difference between the two estimates. Results: We identified 28 new systematic reviews that provided sufficient data for both direct and indirect comparison. After pooling the newly identified cases and previous cases, a total of 55 systematic reviews (with 110 different comparisons) were included. Literature search was systematic in 47 of the 55 reviews. Of the 28 new cases, 17 indicated some efforts to examine trial similarity and 11 mentioned or discussed evidence consistency. Statistically significant discrepancy (p < 0.05) in results between direct and AIC estimate was observed in nine of the 110 comparisons. After excluding any possible non-independent cases, there were four cases of statistically significant discrepancy in 57 independent comparisons. Pooling data from 50 independent comparisons that used odds ratios or risk ratios, the weighted mean discrepancy was -0.117 (SE 0.29), corresponding to a ratio of odds ratios (ROR) of 0.89 (95% CI 0.50 to 1.57). Conclusion: Preliminary results of this updated review of empirical evidence are consistent with the finding from our previous study. The results of adjusted indirect comparison are usually, but not always, in agreement with the results of head-to-head comparison trials.