Despite strong evidence supporting COVID-19 vaccine efficacy and safety, a proportion of the population remains hesitant to receive immunization. Discrete choice experiments (DCEs) can help assess preferences and decision-making drivers. We aim to (1) elicit preferences for COVID-19 vaccines in Canada, Germany, the United Kingdom, and the United States; (2) understand which vaccine attributes people there value; and (3) gain insight into the choices that different population subgroups make regarding COVID-19 vaccines. Participants in the 2019nCoV-408 study were aged ≥18 years; self-reported antivaccinationists were excluded. A DCE with a series of 2 hypothetical vaccine options was embedded into a survey to determine participant treatment preferences (primary objective). Survey questions covered vaccine preference, previous COVID-19 experiences, and demographics, which were summarized using descriptive statistics to understand the study participants' backgrounds. In the DCE, participants were provided choice pairs: 1 set with and 1 without an "opt-out" option. Each participant viewed 11 unique vaccine profiles. Vaccine attributes consisted of type (messenger RNA or protein), level of protection against any or severe COVID-19, risk of side effects (common and serious), and potential coadministration of COVID-19 and influenza vaccines. Attribute level selections were included for protection and safety (degree of effectiveness and side effect risk, respectively). Participants were stratified by vaccination status (unvaccinated, or partially or fully vaccinated) and disease risk group (high-risk or non-high-risk). A conditional logit model was used to analyze DCE data to estimate preferences of vaccine attributes, with the percentage relative importance calculated to allow for its ranking. Each model was run twice to account for sets with and without the opt-out options. The mean age of participants (N=2000) was 48 (SD 18.8) years, and 51.25% (1025/2000) were male. The DCE revealed that the most important COVID-19 vaccine attributes were protection against severe COVID-19 or any severity of COVID-19 and common side effects. Protection against severe COVID-19 was the most important attribute for fully vaccinated participants, which significantly differed from the unvaccinated or partially vaccinated subgroup (relative importance 34.8% vs 30.6%; P=.049). Avoiding serious vaccine side effects was a significantly higher priority for the unvaccinated or partially versus fully vaccinated subgroup (relative importance 10.7% vs 8.2%; P=.044). Attributes with significant differences in the relative importance between the high-risk versus non-high-risk subgroups were protection against severe COVID-19 (38.2% vs 31.5%; P<.000), avoiding common vaccine side effects (12% vs 20.5%; P<.000), and avoiding serious vaccine side effects (9.7% vs 7.5%; P=.002). This DCE identified COVID-19 vaccine attributes, such as protection against severe COVID-19, that may influence preference and drive choice and can inform vaccine strategies. The high ranking of common and serious vaccine side effects suggests that, when the efficacy of 2 vaccines is comparable, safety is a key decision-making factor.