How to optimize the cup orientation in total hip arthroplasty (THA) has been an ongoing question for years. Since Lewinnek suggested a safe zone around 40° inclination and 15° anteversion, various other safe orientations have been proposed in the literature. More recently, the spino-pelvic mobility has been shown to impact the stability of the total hip prosthesis (THP) and should therefore be considered when orienting the cup. Thus we propose a functional safe zone (FSZ) to determine the cup orientations suited to the patient pelvic mobility, evaluated by the pelvic tilts (PTs) in sitting, standing and supine positions. Based on Hsu method*, this FSZ combines the safe zones computed for the three positions. Our goals were (1) to validate the proposed FSZ and (2) to quantify the PTs’ impact on the FSZ mean orientation. A FSZ was computed for 30 patients whose PTs were acquired in sitting, standing and supine positions as part of a clinical study (NCT03555812 in the clinicaltrials.gov database). The FSZ was validated for 10 patients randomly chosen, by comparing the computed FSZ to the “true” FSZ obtained by simulating the motions of a THP 3D model. Both computed and true FSZ were compared in terms of difference of mean anteversion, mean inclination and edges. The correlations between the FSZ mean orientation and the PTs were identified by computing the Pearson correlation coefficients rp and quantified using linear regressions. Correlations were strong if ±rp>0.8, high if ±rp>0.6, moderate if ±rp>0.4 and poor otherwise. The true and computed FSZs differed by -0.2±0.3° (range: -0.6° to 0.4°) for mean anteversion, 0.0±0.1° (range: -0.1° to 0.2°) for mean inclination and 0.2±0.2° (range: 0.0° to 1.0°) for edges. The correlation coefficients and linear regressions between the FSZ mean orientation and the PTs are presented in Figures 1 and 2. To adapt the cup orientation in THA to the patient mobility, we proposed a FSZ computed from the patient PTs in three positions. The FSZ was validated through a simulation study, with mean errors <0.5°. The FSZ mean anteversion was found modified by 0.3° and 0.5° per degree of PT in standing and supine position respectively, and the mean inclination by 0.2° per degree of supine PT. Thus, the more anteverted the pelvis is in these positions, the higher the cup anteversion and inclination should be, and conversely, the more retroverted the pelvis, the lower the anteversion and inclination. While those effects are statistically significant and coherent with the literature, the FSZ mean orientation stays in the Lewinnek safe zone boundaries. However, the size and shape of the FSZ differ from Lewinnek safe zone, thus reducing the margin of error around the optimal orientation (Figure 3). Such observations confirm the need to consider the PTs in different positions before implanting a THP and the usefulness of a FSZ to estimate the optimal cup orientation and its margin of error.