The purpose of this study was to compare treatment satisfaction with triple nucleoside reverse transcriptase inhibitor (NRTI) highly active antiretroviral treatment (HAART) regimens including abacavir (ABC) to HAART regimens that include protease inhibitors (PIs) and to estimate the relationship between patient satisfaction and adherence to HAART. Three open-label clinical trials comparing ABC-including HAART regimens with PI-including HAART regimens were completed, two with patients previously untreated with antiretroviral therapy and one with patients successfully treated with PI-including HAART regimens. The HIV Treatment Satisfaction Questionnaire (HIVTSQ) was completed at several time points during each trial. Levels of patient satisfaction with the ABC and PI regimens were compared for all three trials. The correlation between adherence and patient satisfaction scores was measured using data from an adherence questionnaire in one of the studies. In all three clinical trials, patient satisfaction scores were significantly higher with an ABC-including triple NRTI HAART regimen than with a PI-including HAART regimen. The difference was apparent by week 4 of the trial and was maintained throughout the trial time period. Inspection of the item responses in the patient satisfaction questionnaire indicated that treatment convenience, flexibility, impact on lifestyle, and side effects were key factors in the difference in satisfaction between the treatment groups. In addition, patient satisfaction was shown to be significantly correlated with adherence defined as taking 95% or more of prescribed doses. Greater satisfaction was reported by patients given an ABC-including HAART regimen than those given a PI-including HAART regimen. Patient satisfaction may be an indicator for better treatment adherence.