The ultimate goal of pharmaceutical care is to improve patient HRQOL. Although researchers have attempted successfully to link pharmaceutical care behaviors with HRQOL, the findings are not consistent. Furthermore, the role of patient satisfaction and compliance in this relationship needs to be explored. OBJECTIVE: To test a path analytic model depicting the association of pharmacists’ directive guidance behaviors, patient satisfaction, compliance, and HRQOL. Pharmacists’ directive guidance behaviors were used as an indicator of the level of pharmaceutical care. METHODS: Five ambulatory care pharmacies/clinics were selected for study participation. A fifty-item questionnaire eliciting information about demographics, perception about pharmacists’ directive guidance behaviors, satisfaction with pharmaceutical care behaviors, compliance and HRQOL was administered to volunteers at each study site. A total of 160 patients completed the questionnaire. RESULTS: Bivariate correlations showed that directive guidance behaviors were significantly correlated to patient satisfaction (r=0.56, p<0.001), and SF-12 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores (r=-0.19, p<0.05; r=-0.19, p<0.05, respectively). Also, patient satisfaction was significantly correlated to PCS (r=-0.20, p<0.05). Compliance was significantly correlated to PCS (r=0.25, p<0.01) and MCS (r=0.23, p<0.01). Two path analytic models using PCS and MCS as dependent variables were tested. In path analysis with PCS as the dependent variable, compliance had significant total causal effect of 0.16 (p<0.05) that was due to it’s direct effect. No other path coefficients were significant in this model. In path analysis with MCS as the dependent variable, no path coefficients were significant. CONCLUSIONS: In the two path analytic models evaluated, only patient compliance had a significant direct effect on PCS. Re-specification of the models is needed.