The potential for premolar extractions to produce adverse facial effects after orthodontic treatment is still controversial. Detailed documentation of the predictability, or otherwise, of various soft tissue treatment effects would obviously be of assistance to clinical orthodontists in day-to-day treatment planning, by potentially refining the criteria for appropriate selection of various premolar extraction sequences. With this in mind, a retrospective lateral cephalometric study of 80 premolar extraction cases was undertaken to assess whether different patterns of premolar extraction do in fact produce predictably different lateral profile effects. A comparison was made of the changes in lip curvature after the extractions of all first premolars (4/4), all second premolars (5/5), or upper first and lower second premolars (4/5). Changes in the depths of curvature of both the upper and lower lips were not solely dependent on the selection of a particular premolar extraction sequence. Instead, there were wide ranges of individual variation in the changes in the depths of the lip curves. Therefore, in addition to the inherent soft tissue morphology of the lips in individual patients, it is the combined effect of the lip response to various dental and skeletal changes and the competent clinical management of extraction spaces that apparently affects the shapes of the lips within the lateral profile during treatment. In other words, it would seem possible for the clinician to carefully manage either first or second premolar extraction spaces while still protecting the facial profile.