Control of well drilling operations poses a challenging issue to be tackled. The loss of well control could lead to the occurrence of blowout as a severe threat, involving the risk of human lives and environmental and economic consequences. Conventional proportional-integral (PI) controller is a common practice in the well control operation. The small existing margin between pore pressure and fracture gradients jeopardizes the efficiency of this conventional method to exercise an accurate and precise pressure control. There is a significant incentive to develop more efficient control methodologies to precisely control the annular pressure profile throughout the well bore to ascertain the down-hole pressure environment limits. Adaptive control presents an attractive candidate approach to achieving these demanding goals through adjusting itself to the changes during well drilling operations. The current paper presents a set of adaptive control paradigms in the form of self-tuning control (STC). The developed STC’s are comparatively evaluated on a simulated well drilling benchmark case study for both regulatory and servo-tracking control objectives. The different sets of test scenarios are conducted to represent the superior performance of the developed STC methods compared to the conventional PI control approach.