Purpose: Parametric analysis of 15O-water positron emission tomography (PET) studies allows determination of blood flow (BF), perfusable tissue fraction (PTF), and volume of distribution (Vd) with high spatial resolution. In this paper the performance of basis function and linear least squares methods for generating parametric flow data were evaluated. Procedures: Monte Carlo simulations were performed using typical perfusion values for brain, tumor, and heart. Clinical evaluation was performed using seven cerebral and 10 myocardial 15O-water PET studies. Basis function (BFM), linear least squares (LLS), and generalized linear least squares (GLLS) methods were used to calculate BF, PTF, or Vd. Results: Monte Carlo simulations and human studies showed that, for low BF values (<1 ml min-1ml-1), BF, PTF, and Vd were calculated with accuracies better than 5% for all methods tested. For high BF (>2 ml min-1ml-1), use of BFM provided more accurate Vd compared with (G)LLS. Conclusions: In general, BFM provided the most accurate estimates of BF, PTF, and Vd.