Abstract Purpose Dynamic positron emission tomography (PET) protocols allow for accurate quantification of [¹⁸F]flortaucipir-specific binding. However, dynamic acquisitions can be challenging given the long required scan duration of 130 min. The current study assessed the effect of shorter scan protocols for [¹⁸F]flortaucipir on its quantitative accuracy. Procedures Two study cohorts with Alzheimer’s disease (AD) patients and healthy controls (HC) were included. All subjects underwent a 130-min dynamic [¹⁸F]flortaucipir PET scan consisting of two parts (0–60/80–130 min) post-injection. Arterial sampling was acquired during scanning of the first cohort only. For the second cohort, a second PET scan was acquired within 1–4 weeks of the first PET scan to assess test-retest repeatability (TRT). Three alternative time intervals were explored for the second part of the scan: 80–120, 80–110 and 80–100 min. Furthermore, the first part of the scan was also varied: 0–50, 0–40 and 0–30 min time intervals were assessed. The gap in the reference TACs was interpolated using four different interpolation methods: population-based input function 2T4k_V_B (POP-IP_2T4k_V_B), cubic, linear and exponential. Regional binding potential (BP_ND) and relative tracer delivery (R₁) values estimated using simplified reference tissue model (SRTM) and/or receptor parametric mapping (RPM). The different scan protocols were compared to the respective values estimated using the original scan acquisition. In addition, TRT of the RPM BP_ND and R₁ values estimated using the optimal shortest scan duration was also assessed. Results RPM BP_ND and R₁ obtained using 0–30/80–100 min scan and POP-IP_2T4k_V_B reference region interpolation had an excellent correlation with the respective parametric values estimated using the original scan duration (r² > 0.95). The TRT of RPM BP_ND and R₁ using the shortest scan duration was − 1 ± 5 % and − 1 ± 6 % respectively. Conclusions This study demonstrated that [¹⁸F]flortaucipir PET scan can be acquired with sufficient quantitative accuracy using only 50 min of dual-time-window scanning time.