The pulmonary artery catheter (PAC) remains the gold standard to calculate Fick cardiac outputs (FCOs) in patients with heart failure admitted to the intensive care unit (ICU). The peripherally inserted central catheter (PICC) provides long-term intravenous access and is used outside the ICU; however, there is scant literature validating venous oxygen saturations (VOSs) from PICC lines. Heart failure patients in the ICU with an existing PAC requiring a PICC line to transition were enrolled. Three blood samples were taken per person (1 at PICC, 1 at central venous pressure [CVP], and 1 at distal PAC). We performed repeated measures analysis of variance, as well as reliability analysis on 31 subjects (77% male, 71% Caucasian, mean ± standard deviation age 60 ± 8 years, 80% on inotropes). The average VOSs were 62 ± 11%, 62 ± 12%, and 61 ± 9% for the PICC line, CVP, and distal port, respectively (p = 0.66); there was excellent reliability (0.79). The median FCOs were 5 [4, 6], 5 [4, 6], and 5 [4, 6] L/min at the PICC, CVP, and distal port, respectively (p = 0.91); there was fair-to-good reliability (0.67). In conclusion, VOS and FCO did not differ by location, on average. Reliable data may be obtained through the PICC line, after evaluation from the PAC. The PICC may provide longer-term hemodynamic assessment while improving patient comfort.