Instrumental variable analyses are increasingly used in epidemiologic studies. For dichotomous exposures and outcomes, the typical 2-stage least squares approach produces risk difference estimates rather than relative risk estimates and is criticized for assuming normally distributed errors. Using 2 example drug safety studies evaluated in 3 cohorts from Pennsylvania (1994-2003) and British Columbia, Canada (1996-2004), the authors compared instrumental variable techniques that yield relative risk and risk difference estimates and that are appropriate for dichotomous exposures and outcomes. Methods considered include probit structural equation models, 2-stage logistic models, and generalized method of moments estimators. Employing these methods, in the first study the authors observed relative risks ranging from 0.41 to 0.58 and risk differences ranging from -1.41 per 100 to -1.28 per 100; in the second, they observed relative risks of 1.38-2.07 and risk differences of 7.53-8.94; and in the third, they observed relative risks of 1.45-1.59 and risk differences of 3.88-4.84. The 2-stage logistic models showed standard errors up to 40% larger than those of the instrumental variable probit model. Generalized method of moments estimation produced substantially the same results as the 2-stage logistic method. Few substantive differences among the methods were observed, despite their reliance on distinct assumptions.