Background: Policy decisions about opt-in and opt-out consent for organ donation are based on limited evidence. To fill this gap we investigated the difference between deceased and living organ donation rates in opt-in and opt-out consent systems across a 13 year period. We controlled for extensive covariates and estimated the causal effect of consent with instrumental variables analysis. Method: This panel study used secondary data analysis to compare organ donor and transplant rates in 48 countries that had either opt-in or opt-out consent. Organ donation data were obtained over a 13-year period between 2000 and 2012. The main outcome measures were the number of donors, number of transplants per organ and total number (deceased plus living) of kidneys and livers transplanted. The role of consent on donor and transplant rates was assessed using multilevel modeling and the causal effect estimated with instrumental variables analysis. Results: Deceased donor rates (per-million population) were higher in opt-out (M = 14.24) than opt-in consent countries (M = 9.98;. = -4.27, 95% confidence interval (CI) = -8.08, -0.45, P =.029). However, the number of living donors was higher in opt-in (M = 9.36) than opt-out countries (M = 5.49; B = 3.86, 95% CI = 1.16, 6.56, P =.006). Importantly, the total number of kidneys transplanted (deceased plus living) was higher in opt-out (M = 28.32) than opt-in countries (M = 22.43; B = -5.89, 95% CI = -11.60, -0.17, P =.044). Similarly, the total number of livers transplanted was higher in opt-out (M = 11.26) than opt-in countries (M = 7.53; B = -3.73, 95% CI = -7.47, 0.01, P =.051). Instrumental variables analysis suggested that the effect of opt-in versus opt-out consent on the difference between deceased and living donor rates is causal. Conclusions: While the number of deceased donors is higher than the number of living donors, opt-out consent leads to a relative increase in the total number of livers and kidneys transplanted.