Parafluorofentanyl (4-fluorofentanyl, pFF) is an opioid analgesic analogue of fentanyl developed by Janssen Pharmaceuticals in the 1960s.

[1] 4-Fluorofentanyl was sold briefly on the US black market in the early 1980s,[citation needed] before the introduction of the Federal Analog Act which for the first time attempted to control entire families of drugs based on their structural similarity rather than scheduling each drug individually as they appeared.

[2] 4-Fluorofentanyl is made by the same synthetic route as fentanyl, but by substituting para-fluoroaniline for aniline in the synthesis.

Fentanyl analogs have killed thousands of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear.

[4] In 2020, the Drug Enforcement Agency warned about the increasing prevalence of parafluorofentanyl in Arizona.