The United States is in the midst of an opioid overdose epidemic. A prior report using the Center for Disease Control’s Wide-ranging Online Data for Epidemiologic Research (WONDER) database discovered that opioid overdoses decreased by 24.8% from 1999 to 2010 in states with medical cannabis (MC+) relative to those without (MC−). The present study evaluated any differences following MC legislation on WONDER reported opioid overdoses, corrected for population, from 1999 to 2017 using an interrupted time series. Overdoses were significantly higher in MC+ states from 2012-2017. The slope of opioid overdose deaths over time increased significantly post-implementation in states without MC (3-years Pre = 0.1 ± 0.1, 3-years Post = 0.7 ± 0.2, t(16) = 2.88, p ≤ .011). Overdose deaths showed a non-significant elevation in states with MC (Pre = 1.3 ± 0.3, Post = 2.8 ± 0.8, t(11) = 2.01, p = .069). Post-legalization slopes were significantly higher in MC+ than MC− (t(11.95) = 2.70, p < .05). Overall, any impact of medical cannabis laws on opioid overdoses appears modest. There are other confounds (e.g. death determination reporting quality) which differ non-randomly among states and are non-trivial to account for in ecological investigations of cannabis policy. Alternatively, the potency of fentanyl analogues may obscure any protective effects of MC against illicit opioid harms.