© 2016 Wiley Periodicals, Inc. Objective: To describe a novel real-time ultrasound (US)-guided distal superficial femoral vein (DSFV) cannulation technique for insertion of peripherally inserted central catheters (PICC) in critically ill infants with congenital heart disease. Design: Descriptive retrospective cohort study. Setting: Pediatric cardiac intensive care unit in a pediatric tertiary hospital. Patients: First 28 critically ill infants that received DSFV PICCs via this new technique. Results: Thirty-seven US-guided DSFV PICCs were attempted on 31 infants from September 2012 to November 2014; 34 PICCs were placed in 28 patients (success rate 92%). Twenty-six of 28 patients underwent cardiac surgery. Median (IQR) age at time of PICC placement 39 days (13, 151); weight 3.4 kg (3.2, 5.3). 25/34 PICCs were placed in patients with STAT 4 or 5 category. Median PICC duration 16 days (11, 29); maximum duration 123 days. Ten infants (36%) had DSFV PICCs placed as the primary central venous access in perioperative period. Ten of 28 patients underwent cardiac catheterization while DSFV PICC was in place, four of which were performed through ipsilateral common femoral vein. Two patients had femoral arterial lines placed in the ipsilateral femoral artery while DSFV PICC was in place. There were no reported inadvertent arterial punctures. The PICC-associated infection rate was 4.6 per 1000 line days. Four of 34 DSFV PICCs (11.8%) were associated with deep venous thrombosis. Conclusions: DSFV is a novel venous access site for PICC placement with high success rate and sufficient longevity and flexibility for critically ill infants with cardiac disease. More experience and larger studies are needed to confirm its potential advantages.