Background To offer support for patients who decide to discontinue antipsychotic and antidepressant medication, identifying which potentially modifiable factors correlate with discontinuation success is crucial. Here, we analyzed the predictive value of the professional support received, circumstances prior to discontinuation, a strategy of discontinuation, and use of functional and non-functional coping strategies during discontinuation on self-reported discontinuation success and on objective discontinuation. Methods Patients who had attempted discontinuing antipsychotics (AP) and/or antidepressants (AD) during the past 5 years (n = 316) completed an online survey including questions on subjective and objective discontinuation success, sociodemographic, clinical and medication-related factors, and scales to assess the putative predictors. Results A regression model with all significant predictors explained 20–30% of the variance in discontinuation success for AD and 30–40% for AP. After controlling for baseline sociodemographic, clinical and medication-related factors, the most consistent predictor of subjective discontinuation success was self-care behavior, in particular mindfulness, relaxation and making use of supportive relationships. Other predictors depended on the type of medication: For AD, good alliance with the prescribing physician predicted higher subjective success whereas gradual tapering per se was associated with lower subjective success and a lower chance of full discontinuation. In those tapering off AP, leaving time to adjust between dose reductions was associated with higher subjective success and fewer negative effects. Conclusions The findings can inform evidence-based clinical guidelines and interventions aiming to support patients during discontinuation. Further studies powered to take interactions between variables into account are needed to improve the prediction of successful discontinuation.