In percutaneous transluminal coronary angioplasty (PTCA), prolonged balloon inflations using perfusion balloon catheters have shown a higher procedural success rate and fewer in-hospital complications than short balloon inflations. However, perfusion balloons have well-recognized limits for routine use. This study assessed the effects of a prolonged cumulative occlusion time obtained with sequential balloon inflations using a routine balloon catheter, applicable to all lesions, and compared these results with those obtained with standard short balloon inflations. Three hundred ten lesions (in 289 patients) were randomized to either standard (3 to 5 inflations ≤1 minute each; n = 161) or prolonged (3 to 5 inflations of 3 to 5 minutes each; n = 149) balloon inflations. Angiographic success (residual stenosis < 50% and no dissection ≥D1) was assessed at the end of this “protocol” phase. Further dilatation was performed if required (“adjuncfive” phase). Systematic repeat catheterization was scheduled 4 to 6 months later. Cumulative inflation time was 198 ± 58 seconds in the “standard” group versus 782 ± 303 seconds in the “prolonged” group. At the end of the protocol phase, the success rate was higher after prolonged than after standard dilatation (92% vs 80%; p < 0.002), with less frequent dissections (14% vs 30%; p = 0.0009). At the end of the adjunctive phase, required for 12 patients in the prolonged group and 32 patients in the standard group (p = 0.003), results were comparable in the 2 groups and the restenosis rate was similar at 6 months. The prolonged cumulative occlusion time achieved with sequential balloon inflations using a routine balloon catheter improves the immediate results of PTCA. Repeat catheterization shows no effect of prolonged sequential inflations on the restenosis rate.