To shorten hospital stay or to allow ambulatory procedures, 4Fr catheters for left-sided cardiac catheterization can be used. These latter parameters may also be influenced by compression time and bed rest duration. The role of these parameters was assessed by prospectively including 130 consecutive patients who underwent 4Fr femoral diagnostic procedures. The patients were randomized into two groups: group 1 consisted of 70 patients undergoing 5-minute compression and group 2 consisted of 60 patients with 15-minute compression. In each group, a second randomization was applied to determine the bed rest duration (2-4 hours). More group 1 patients experienced immediate bleeding following manual compression than group 2 patients (12 [17%] vs 3 [5%], P < 0.03, respectively). Compared to group 2, a slight but nonsignificant increase in the total number of hematomas was observed in group 1 (31 vs 22%, NS). No difference existed in terms of local large hematomas at 24 hours (7% in each group) or in terms of benign > or = 10 cm diffuse subcutaneous ecchymosis at 7-day follow-up (13 [19%] group 1 patients vs 8 [13%] group 2 patients, NS). However, persistence of diffuse subcutaneous ecchymosis at 7-day follow-up appeared to be related to the history of immediate bleeding following manual compression in both groups (group 1: 5/13 vs 7/57 patients [P < 0.04] and group 2: 3/8 vs 0/52 patients [P < 0.002]). In conclusion, 4Fr femoral left-sided cardiac catheterization is safe and could be performed as an ambulatory procedure. However, it requires 15-minute duration of manual compression associated with 2-hour bed rest to decrease local bleeding complications.