To evaluate the safety and effectiveness of the optical coherence tomography-guided Ocelot catheter to cross femoropopliteal chronic total occlusions (CTOs).The CONNECT II study was a prospective, multicenter, non-randomized single-arm study of the safety and effectiveness of the Ocelot catheter in CTO crossing. Key inclusion criteria were a 99% to 100% stenosed femoropopliteal segment, lesion length between 1 and 30 cm, and resistance to guidewire crossing. The main exclusion criterion was a severely calcified target vessel. The primary safety endpoint was 30-day major adverse events (MAE), while the primary effectiveness endpoint was successful CTO crossing (i.e., guidewire placement in the distal true lumen) with the Ocelot catheter. Endpoint analysis was based on pre-specified objective performance criteria. Between February and June 2012, 100 patients (55 men; mean age 69 years) were enrolled. Most of the CTOs (94%) were in the superficial femoral artery (SFA); mean lesion length was 16.6±9.3 cm.Through 30 days, 2 patients experienced MAE (significant perforations) related to the Ocelot catheter. The Ocelot catheter successfully crossed 97% of target CTOs either alone (72%), in conjunction with an assist device (18%), or in conjunction with a re-entry device (7%). Both primary safety and effectiveness endpoints were met.The Ocelot catheter with optical coherence tomography guidance offers physicians a reliable option for crossing femoral and popliteal chronic total occlusions with low MAE rates.