Although several studies have documented challenges related to inadequate adherence to antiretroviral therapy (ART) and high loss to follow-up (LTFU) among Option B+ women, there is limited understanding of why these challenges occur and how to address them. This qualitative study examines women’s experiences with ART adherence and retention in care. Between July and October 2015, in-depth interviews were conducted with 39 pregnant and lactating women who initiated ART at Bwaila Hospital in Lilongwe, Malawi. Study participants included 14 in care and 25 out of care women, according to facility records. Data were analyzed using an inductive, open-coding approach to thematic analysis. Ten of the respondents (7 out of care, 3 in-care) had stopped and re-started treatment before the interview date. One of the most important factors influencing adherence and retention was the strength of women’s support systems. In contrast to women in-care, most out-of-care women lacked emotional and financial support from male partners, received minimal counseling from providers at initiation, lacked designated guardians to assist with medication refills or clinic appointments, and were highly mobile. Mobility led to difficulties in accessing treatment in new settings. The most common reasons women re-started treatment following interruptions were due to providers’ counseling and encouragement and the mother’s desire to be healthy. Improved counseling at initiation, active follow-up counseling, women’s economic empowerment interventions, promotion of peer counseling schemes and meaningful engagement of male partners can help in addressing the identified barriers and promoting sustained retention of Option B+ women.