A prospective phase II study examined the safety and efficacy of venetoclax combined with low-dose cytarabine (LDAC) in AML at first measurable residual disease (MRD) or oligoblastic relapse.Patients with either MRD (≥1 log rise) or oligoblastic relapse (blasts 5%-15%) received venetoclax 600 mg once daily D1-28 plus LDAC once daily D1-10 in 28-day cycles. The primary objective was MRD response in the MRD relapse cohort or complete remission (CR/CRh/CRi) in the oligoblastic relapse cohort.Forty-eight adults with either MRD (n = 26) or oligoblastic (n = 22) relapse were enrolled. Median age was 67 years (range, 18-80) and 94% had received previous intensive chemotherapy. Patients received a median of four cycles of therapy; 17% completed ≥12 cycles. Patients with oligoblastic relapse had more grade ≥3 anemia (32% 4%; = .02) and infections (36% 8%; = .03), whereas grade 4 neutropenia (32 23%) or thrombocytopenia (27 15%) were comparable with the MRD relapse cohort. Markers of molecular MRD relapse included mutant (77%), (4%), (4%), or (4%). Three patients with a log rise in / (12%) were included. By cycle 2 in the MRD relapse cohort, a log reduction in MRD was observed in 69%; 46% achieved MRD negative remission. In the oligoblastic relapse cohort, 73% achieved CR/CRh/CRi. Overall, 21 (44%) underwent hematopoietic cell transplantation. Median overall survival (OS) was not reached in either cohort. Estimated 2-year OS rate was 67% (95% CI, 50 to 89) in the MRD and 53% (95% CI, 34 to 84) in the oligoblastic relapse cohorts.For AML in first remission and either MRD or oligoblastic relapse, venetoclax plus LDAC is well tolerated and highly effective.