Polyetheretherketone (PEEK) is considered a 'gold-standard' material choice for cranial bone reconstruction. The introduction of additive manufacturing (AM) into the pipeline for patient specific cranial implant (PSCI) fabrication could accelerate supply chain needs and improve patient outcomes. Fused filament fabrication (FFF), a material extrusion-based technology, is a much-researched process due to its accessibility and ease of use. However, the quality of PEEK processed by FFF is highly affected by the applied printing profile. Therefore, in this study, the effects of printing parameters such as build orientation and air flow temperature on mechanical performance (cyclic and impact tests) and implant quality (characterisation of surface topography, discoloration and crystallinity) were analysed and compared with a commercial milled PEEK implant. It has been found that horizontally printed implants show higher mechanical integrity compared to implants printed upright or tilted by 45°, but obtain lower surface quality. In addition, lower air flow temperatures lead to strong implant discolorations due to high amounts of amorphousness, which further result in high absorbed energies during impact as well as large deformations until complete failure. The best results from a mechanical point of view were achieved with PSCIs printed at a build orientation of 180°, an air flow temperature of 210 °C, a shell number of 3, a layer height of 0.15 mm, a printing speed of 50 mm/min, a rectilinear ±45° infill pattern and an implant thickness of 5 mm. However, the surface quality of implants produced this way is not completely satisfactory, and the arrangement of the support structures must be further improved.