We evaluated the effectiveness of short-term cash and food assistance to improve adherence to antiretroviral therapy (ART) and retention in care among people living with HIV in Tanzania. At three clinics, 805 participants were randomized to three groups in a 3 : 3 : 1 ratio, stratified by site : nutrition assessment and counseling (NAC) and cash transfers (∼$11/month, n = 347), NAC and food baskets (n = 345), and NAC-only (comparison group, n = 113, clinicaltrials.gov NCT01957917). Eligible people living with HIV were at least 18 years, initiated ART 90 days or less prior, and food insecure. Cash or food was provided for 6 or less consecutive months, conditional on visit attendance. The primary outcome was medication possession ratio (MPR) at least 95% at 6 months. Secondary outcomes were appointment attendance and loss to follow-up (LTFU) at 6 and 12 months. The primary intent-to-treat analysis included 800 participants. Achievement of MPR at least 95% at 6 months was higher in the NAC + cash group compared with NAC-only (85.0 vs. 63.4%), a 21.6 percentage point difference [95% confidence interval (CI): 9.8, 33.4, P < 0.01]. MPR at least 95% was also significantly higher in the NAC + food group vs. NAC-only (difference = 15.8, 95% CI: 3.8, 27.9, P < 0.01). When directly compared, MPR at least 95% was similar in the NAC + cash and NAC + food groups (difference = 5.7, 95% CI: -1.2, 12.7, P = 0.15). Compared with NAC-only, appointment attendance and LTFU were significantly higher in both the NAC + cash and NAC + food groups at 6 months. At 12 months, the effect of NAC + cash, but not NAC + food, on MPR at least 95% and retention was sustained. Short-term conditional cash and food assistance improves ART possession and appointment attendance and reduces LTFU among food-insecure ART initiates in Tanzania.