The detection of novel fentanyl analogs in both seized drugs and toxicological specimens has presented a significant challenge to laboratories with respect to identification, sourcing reference drug standards, time required for method development and ensuring sufficient method sensitivity. The New York City Office of Chief Medical Examiner (NYC OCME) has included testing for valerylfentanyl as part of a panel of synthetic opioids since May 2017 but did not identify the first valerylfentanyl positive case until July 2018. Unlike many other illicit fentanyl analogs that were briefly identified before being replaced with a new analog, valerylfentanyl has persisted over time and continues to be identified in New York City acute polydrug intoxications. Since July 2018, a total of 69 cases were identified with valerylfentanyl present, but there were no cases where it was the sole intoxicant. 84% of decedents were male, with the majority between the ages of 50 and 59 years (39%) and were predominantly Hispanic (49%). The cause of death in all 69 cases involved acute polydrug intoxication, while the manner of death was deemed an accident in 68 cases and undetermined in one case. Concentrations of valerylfentanyl in postmortem blood ranged from < 0.10 to 21 ng/mL with 44.9% (N = 31) of the concentrations at or below the lower limit of quantification (0.10 ng/mL) but above the limit of detection (0.05 ng/mL). Fentanyl was present in 100% of the cases and in higher concentrations (1.6–116 ng/mL). The most common drug classes detected with valerylfentanyl were other opiates (76.8%), cocaine/metabolites (50.7%), benzodiazepines (29%), and ethanol (21.7%). Valerylfentanyl is a relatively unknown fentanyl analog with limited information in the scientific literature. This study presents the first publication detailing a series of postmortem cases involving valerylfentanyl in acute intoxications and includes key demographic information and femoral blood concentrations for improved interpretation and analysis.