In 2006 the Mexican government launched an aggressive campaign to weaken drug-trafficking organizations (DTOs). The security policies differed significantly from those of previous administrations in the use of a leadership strategy (the targeting for arrest of the highest levels or core leadership of criminal networks). While these strategies can play an important role in disrupting the targeted criminal organization, they can also have unintended consequences, increasing inter-cartel and intra-cartel fighting and fragmenting criminal organizations. What impact do captures of senior drug cartel members have on the dynamics of drug-related violence? Does it matter if governments target drug kingpins vs. lower ranked lieutenants? We analyze whether the captures or killings of kingpins and lieutenants have increased drug-related violence and whether the violence spills over spatially. To estimate effects that are credibly causal, we use different empirical strategies that combine difference-in-differences and synthetic control group methods. We find evidence that captures or killings of drug cartel leaders have exacerbating effects not only on DTO-related violence, but also on homicides that affect the general population. Captures or killings of lieutenants, for their part, only seem to exacerbate violence in “strategic places” or municipalities located in the transportation network. While most of the effects on DTO-related violence are found in the first six months after a leader’s removal, effects on homicides affecting the rest of the population are more enduring, suggesting different mechanisms through which leadership neutralizations breed violence.