Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor for 6-12 months is the current standard treatment for patients after percutaneous coronary intervention (PCI). However, the optimal DAPT duration is still under debate. A novel strategy with P2Y12 inhibitor monotherapy after PCI has been proposed recently. This strategy shortens the duration of DAPT to 1 to 3 months, followed by monotherapy with a P2Y12 inhibitor instead of aspirin. It has been tested in several clinical trials with promising results. In this article, we reviewed the relevant clinical trial data and the scientific rationale of P2Y12 inhibitor monotherapy with laboratory evidence of platelet inhibition. An early aspirin-free strategy with P2Y12 inhibitor monotherapy seems feasible in some of the patients after PCI.