The purpose of this study was to assess treatment margins in free-breathing irradiation of pancreatic cancer after bone alignment, and evaluate their impact on conformal radiotherapy. Fifteen patients with adenocarcinoma of the head of the pancreas underwent implantation of single fiducial marker. Intrafraction uncertainties were assessed on simulation four-dimensional computed tomography (4D CT) by calculating maximal intrafraction fiducial excursion (MIFE). In the first ten patients, after bony alignment, the position of the fiducial was identified on weekly acquired megavolt cone-beam CT (MV-CBCT). The interfraction residual uncertainties were estimated by measuring the fiducial displacements with respect to the position in the first session. Patient mean (pM) and patient standard deviation (pSD) of fiducial displacement, mean (μM) and standard deviation (μSD) of pM, and root-mean-square of pSD (σ(res)) were calculated. In the other five patients, MIFE was added to the residual component to obtain personalized margin. In these patients, conformal kidney sparing (CONKISS) irradiation was planned prescribing 54/45 Gy to PTV1/PTV2. The organ-at-risk limits were set according to current NCCN recommendation. No morbidity related to the fiducial marker implantation was recorded. In the first ten patients, along right-left, anterior-posterior, and inferior-superior directions, MIFE was variable (mean ± std = 0.24 ± 0.13 cm, 0.31 ± 0.14 cm, 0.83 ± 0.35 cm, respectively) and was at most 0.51, 0.53, and 1.56 cm, respectively. Along the same directions, μM were 0.09, -0.05, -0.05 cm, μSD were 0.30, 0.17, 0.33 cm, and σ(res) were 0.35, 0.26, and 0.30 cm, respectively. MIFE was not correlated with pM and pSD. In the five additional patients, it was possible to satisfy recommended dose limits, with the exception of slightly higher doses to small bowel. After bony alignment, the margins for target expansion can be obtained by adding personalized MIFE to the residual interfraction term. Using these margins, conformal free-breathing irradiation is a reliable option for the treatment of pancreatic cancer.