The goal of this study was to use linear optimization techniques as a systematic method of cine phase contrast pulse sequence design and to apply this technique to the measurement of blood flow in vivo. The optimized waveforms were validated in a constant flow phantom with average velocities ranging from 5 to 50 cm/s. The same optimized sequence was also run in a segmented k-space variation with five phase encoding lines per segment. The magnetic resonance (MR) derived velocity measurements were accurate over the entire range of velocities tested (p < .05) in both cases. The same optimized pulse sequence was applied to the measurement of flow in main pulmonary artery of five normal volunteers and compared with stroke volumes and cardiac outputs calculated from right ventricular volume measurements. These measurements showed a mean difference between the MR phase contrast calculated stroke volume and the volumetric stroke volume measurement of 9.8 +/- 11.6%. The mean difference between the calculated phase contrast cardiac output and the volumetric cardiac output was 4.4 +/- 10%. These results imply that optimization techniques are an efficient method for designing cine phase contrast pulse sequences.