People with serious mental illness may require long-term psychotropic medications. However, nonadherence is prevalent after discharge, often leading to re-admission. Several strategies exist to reduce nonadherence. The current project uses clinical practice improvement methodologies to test and adjust strategies to improve medication adherence at the Institute of Mental Health in Singapore.Two focus groups (one of which involved nonadherent individuals and the other adherent individuals) were conducted to explore the root cause of our service users' nonadherence. On the basis of the causes identified, the team developed and implemented a person-centered medication adherence counseling intervention, incorporating motivational interviewing and psychoeducation. Data from all service users (n=156) who were nonadherent to psychotropic medications upon admission to our men's ward between October 2017 and December 2018 were examined, with 63 of the men serving as the baseline sample and 93 receiving the adherence intervention. The team also reduced medication frequency and actively explored patients' willingness to switch to long-acting injectable antipsychotics. A validated visual analogue self-reporting scale was used to measure adherence at screening and 30 days after discharge. Interrupted time series analysis was used to assess the effects.After an intervention involving 3 specific strategies that addressed the concerns identified during the focus groups, the percentage of people who adhered to their treatment regimen 30 days after discharge increased by 33% (95% confidence interval: 15%-51%, P=0.001). Our balance measure (a secondary outcome that may be negatively or positively affected by efforts to influence the primary outcome), which was the percentage of people readmitted within 30 days of their discharge, showed a significant improvement (ie, a decrease in percentage readmitted).Quality improvement methodologies can be used to solve common problems with context-specific solutions. The implementation of person-centered medication adherence counseling led by an advanced practice nurse in concert with optimization of medication regimens appears to be a promising strategy for improving adherence in nonadherent patients admitted to the psychiatric ward.