Cognitive-behavioural models of compulsive checking posit a dominant role for beliefs regarding one’s responsibility to prevent harm. In the current study we employed a computerised cognitive bias modification of interpretation (CBM-I) paradigm to target and modify responsibility biases in a sample of undergraduate students with high levels of checking symptoms (N = 100). Participants were randomly assigned to either a positive (decrease responsibility bias) or negative (increase responsibility bias) CBM-I training condition. Relative to participants in the negative training condition, participants in the positive training condition demonstrated reduced responsibility bias in a subsequent interpretive bias test. Positive training also resulted in more adaptive physiological responding during a responsibility stressor task. There were no differential effects of CBM-I training, however, on observed or self-reported checking or self-reported responsibility beliefs. In light of these mixed findings, we outline future avenues for improving the efficacy of CBM-I training targeting responsibility biases.