The study combined quantitative and qualitative approaches, in terms of both staff perception and facility manager perspective, to evaluate the effectiveness of indoor environmental quality (IEQ) of LEED–certified facilities and relationship between IEQ and occupant comfort and productivity in healthcare settings in the USA climate zones 2 and 3. A multiple-methods approach combining a questionnaire survey and semi-structured interview was tested for effective post-occupancy evaluation. The study compared one non-LEED healthcare facility with five LEED certified healthcare buildings and examined which variable(s) had significant relationship with comfort and productivity by surveying 249 occupants and interviewing six facility managers in six healthcare settings. The results showed that five LEED–certified healthcare settings were superior to one non-LEED facility in most of building performance factors. Building design, temperature comfort, image presented to visitors, use of space, control over noise and ability to meet occupants’ needs were significant predictors for overall comfort. Lighting overall, temperature comfort and image presented to visitors had a significant positive relationship with perceived productivity. Only one non-LEED hospital was selected and some buildings had small response rate, the results should be interpreted with caution.