Lower limb amputation is a life-changing event that can cause significant disruptions in many important areas of existence. Although a substantial minority of individuals suffer from emotional difficulties following this procedure, most adapt successfully to the losses and limitations incurred, with some achieving positive change and growth as a result. According to self-regulation theory, the physical, social and psychological upheaval caused by amputation is likely to disturb progress towards goal attainment, which may leave individuals vulnerable to negative psychosocial outcomes if they do not regulate their goals in response to these challenges. The aim of the present study was to examine the relationships between goal disturbance, tenacious goal pursuit (TGP), flexible goal adjustment (FGA), and various positive and negative psychosocial outcomes (participation, positive and negative affect, quality of life, psychosocial adjustment to amputation, depressive symptomatology) in a sample of 98 individuals with lower limb amputations, and to investigate whether these self-regulatory constructs predicted psychosocial outcomes in this population after controlling for sociodemographic/clinical variables, optimism, and perceived social support. Participants completed self-report questionnaires on admission to an inpatient prosthetic rehabilitation programme (T1), six weeks post-discharge (T2), and six months post-discharge (T3). Baseline assessments of the self-regulatory constructs together contributed significantly to the prediction of several psychosocial outcomes at each time point. Higher levels of goal disturbance predicted poorer outcomes at T1, whereas TGP and FGA were predictive of enhanced outcomes at each study time point. These findings indicate the utility of self-regulation theory as an organising framework for research on psychosocial adjustment to amputation. TGP and FGA may help in identifying individuals at risk for long-term adjustment difficulties following limb loss, and represent important targets for interventions to promote adjustment in this patient group.