Background International drug law enforcement agencies have identified an apparent rise in high level drug traffickers choosing to deal in multiple different drugs. It is hypothesised that this may be a “deliberate modus operandi” and that the formation of “portfolios of trades” may make such traffickers more profitable, harmful and resilient to changes in drug supply and policing. In this paper we provide the first exploration of the extent, nature and harms of poly-drug trafficking at Australian borders. Methods Two different methods were used. First, we used Australian Federal Police (AFP) data on all commercial level seizures at the Australian border from 1999 to 2012 to identify the proportion of seizures that were poly-drug and trends over time. Second, we used unit-record data on a sub-set of 20 drug trafficking cases and linked-cases (defined as the original drug trafficking case and all other criminal cases that were connected via common offenders and/or suspects) to compare the profiles of poly-drug and mono-drug traffickers, including: the total weight and type of drug seized, the value of assets seized, and the level of involvement in other crime (such as money laundering and corruption). Results Between 5% and 35% of commercial importations at the Australian border involved poly-drug trafficking. Poly-drug trafficking occurred in almost every year of analysis (1999–2012), but it increased only slightly over time. Compared to mono-drug traffickers poly-drug traffickers were characterised by: larger quantities of drugs seized, larger networks, longer criminal histories and more involvement in other types of serious crime. Conclusion Some fears about poly-drug traffickers may have been overstated particularly about the inherent escalation of this form of trafficking. Nevertheless, this suggests poly-drug traffickers are likely to pose added risks to governments and law enforcement than mono-drug traffickers. They may necessitate different types of policy responses.