The web-based delivery of psychosocial interventions is a promising treatment modality for people suffering from chronic pain, and other forms of physical and mental illness. Despite the promising findings of first studies, patients may vary in the benefits they draw from self-managing a full-blown web-based psychosocial treatment. We lack knowledge on moderators and predictors of change during web-based interventions that explain for whom web-based interventions are especially (in)effective. In this study, we primarily explored for which chronic pain patients web-based Acceptance and Commitment Therapy (ACT) was (in)effective during a large three-armed randomized controlled trial. Besides standard demographic, physical and psychosocial factors we focused on positive mental health. Data from 238 heterogeneously diagnosed chronic pain sufferers from the general Dutch population following either web-based ACT (n = 82), or one of two control conditions [web-based Expressive Writing (EW; n = 79) and Waiting List (WL; n = 77)] were analysed. ACT and EW both consisted of nine modules and lasted nine to 12 weeks. Exploratory linear regression analyses were performed using the PROCESS macro in SPSS. Pain interference at 3-month follow-up was predicted from baseline moderator (characteristics that influence the outcome of specific treatments in comparison to other treatments) and predictor (characteristics that influence outcome regardless of treatment) variables. The results showed that none of the demographic or physical characteristics moderated ACT treatment changes compared to both control conditions. The only significant moderator of change compared to both EW and WL was baseline psychological wellbeing, and pain intensity was a moderator of change compared to EW. Furthermore, higher pain interference, depression and anxiety, and also lower levels of emotional well-being predicted higher pain interference in daily life 6 months later. These results suggest that web-based self-help ACT may not be allocated to chronic pain sufferers experiencing low levels of mental resilience resources such as self-acceptance, goals in life, and environmental mastery. Other subgroups are identified that potentially need specific tailoring of (web-based) ACT. Emotional and psychological wellbeing should receive much more attention in subsequent studies on chronic pain and illness.