The acute coronary syndrome (ACS) patients who are not ready to quit smoking immediately have an extremely low rate of cessation. This study aims to investigate the efficacy of intensive personalized '5As+5Rs'intervention (IPANR intervention) on smoking cessation in this population. A parallel-group randomized controlled trial was carried out, which compared IPANR intervention with routine 5Rs (control) at Fu Xing Hospital, Capital Medical University, Bei Jing, China. Three hundred and twenty hospitalized ACS smokers who were not ready to quit were randomly distributed to IPANR intervention group comprising three individual counseling during hospitalization and 15 intensive follow-up sessions (weekly during months 1, 2, 3, and monthly thereafter until month 6) or 5Rs group in a 1:1 fashion by 8 cardiologists who were blinded to the allocation sequence. Primary end point was carbon monoxide-confirmed continuous abstinence rate (CAR) through week 9 to week 12. Secondary outcome included abstinence rate at 24 weeks. Overall, 97.5% (312/320) participants completed the trial. An intention-to-treat analysis showed statistically significant advantage of IPANR compared with control group at 4 weeks CAR (27.5% vs. 17.5%, RR = 1.571, 95% CI = 1.032-2.392, p = 0.032, number needed to treat (NNT) = 10), and abstinence rate at 24 weeks (23.8% vs.15.0%, RR 1.583, 95% CI = 0.998-2.512, p = 0.048, NNT: 11.36). At 24 weeks, cigarettes smoked per day by the patients who failed to quit were significant lower in IPANR group than 5Rs group (13.21 +/- 8.23 vs. 17.45 +/- 10.71; p < 0.001). The IPANR initiated during hospitalization, is a feasible and effective approach for smoking cessation in ACS patients not ready to quit immediately. Smoking has a major impact on acute stages of ACS for recurrent ischemic events and long-term outcomes. However, there are few evidence-based treatments for smokers who are not ready to quit. This study described a cessation intervention initiated during hospitalization and included 15 intensive follow-up aimed at enabling ACS smokers who were not ready to quit immediately to deliver adequate motivational and behavior change counseling. Given its effectiveness demonstrated in this prospective study, this intervention in hospitalized ACS smokers might have the potential to substantially improve the cessation rate of ACS patients who are not ready to quit smoking immediately.