ImportanceAdherence to selected antihypertensive medications (proportion of days covered [PDC]) declined after guidance to shelter in place for COVID-19.ObjectivesTo determine whether PDC for all antihypertensive medications collectively fell from the 6 months before sheltering guidance (September 15, 2019, to March 14, 2020 [baseline]) compared with the first (March 15 to June 14, 2020) and second (June 15 to September 14, 2020) 3 months of sheltering and to assess the usefulness of baseline PDC for identifying individuals at risk for declining PDC during sheltering.Design, Setting, and ParticipantsThis retrospective cohort study included a random sample of US adults obtained from EagleForce Health, a division of EagleForce Associates Inc. Approximately one-half of the adults were aged 40 to 64 years and one-half were aged 65 to 90 years, with prescription drug coverage, hypertension, and at least 1 antihypertensive medication prescription filled at a retail pharmacy during baseline.Main Outcomes and MeasuresPrescription claims were used to assess (1) PDC at baseline and changes in PDC during the first and second 3 months of sheltering and (2) the association of good (PDC ≥ 80), fair (PDC 50-79), and poor (PDC < 50) baseline adherence with adherence during sheltering.ResultsA total of 27 318 adults met inclusion criteria (mean [SD] age, 65.0 [11.7] years; 50.7% women). Mean PDC declined from baseline (65.6 [95% CI, 65.2-65.9]) during the first (63.4 [95% CI, 63.0-63.8]) and second (58.9 [95% CI, 58.5-59.3]) 3 months after sheltering in all adults combined (P < .001 for both comparisons) and both age groups separately. Good, fair, and poor baseline adherence was observed in 40.0%, 27.8%, and 32.2% of adults, respectively. During the last 3 months of sheltering, PDC declined more from baseline in those with good compared with fair baseline adherence (−13.1 [95% CI, −13.6 to −12.6] vs −8.3 [95% CI, −13.6 to −12.6]; P < .001), whereas mean (SD) PDC increased in those with poor baseline adherence (mean PDC, 31.6 [95% CI, 31.3-31.9] vs 34.4 [95% CI, 33.8-35.0]; P < .001). However, poor adherence during sheltering occurred in 1034 adults (9.5%) with good baseline adherence, 2395 (31.6%) with fair baseline adherence, and 6409 (72.9%) with poor baseline adherence.Conclusions and RelevanceThese findings suggest that individuals with poor baseline adherence are candidates for adherence-promoting interventions irrespective of sheltering guidance. Interventions to prevent poor adherence during sheltering may be more useful for individuals with fair vs good baseline adherence.