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We provide an overview of classical and newer methods for the control of confounding of time-invariant interventions to permit causal inference in public health evaluations.We estimated the causal effect of gender on all-cause mortality in a large HIV care and treatment program supported by the President’s Emergency Program for AIDS Relief in Dar es Salaam, Tanzania, between 2004 and 2012. We compared results from multivariable modeling, three propensity score methods, inverse-probability weighting, doubly robust methods, and targeted maximum likelihood estimation. Considerable confounding was evident, and, as expected by theory, all methods considered gave the same result, a statistically significant approximately 20% increased mortality rate in men.In general, there is no clear advantage of any of these methods for causal inference over classical multivariable modeling, from the point of view of either bias reduction or efficiency. Rather, given sufficient data to adequately fit the multivariable model to the data, multivariable modeling will yield causal estimates with the greatest statistical efficiency. All methods can adjust only for well-measured confounders-if there are unmeasured or poorly measured confounders, none of these methods will yield causal estimates.