This article summarizes the top 20 research studies of 2023 identified as POEMs (patient-oriented evidence that matters) and the most highly rated guidelines. A large randomized controlled trial found that the time antihypertensive medications are taken has no effect on important outcomes. A fixed-dose approach to statin prescribing is not inferior to a treat-to-target strategy for management of lipid levels. Blood pressure measurements using 24-hour ambulatory monitoring are better than office measurements for predicting mortality. In patients 80 years and older with atrial fibrillation, direct oral anticoagulants have fewer harms than vitamin K antagonists and similar benefits. In people at high risk of cardiovascular disease, the Mediterranean and low-fat diets are the better options among seven dietary programs. An observational study of people with acute COVID-19 in the Omicron phase showed that nirmatrelvir/ritonavir was effective in reducing hospitalizations and death. The diagnosis of urinary tract infection requires a higher optimal cutoff to define pyuria on automated microscopy than was thought. A new regimen has been found using one of the most effective treatments for toenail onychomycosis. Dextromethorphan, honey, and inhaled ipratropium do not appear to be effective for acute cough. Serotonin-norepinephrine reuptake inhibitors are effective for some types of pain syndromes. In a 6-week trial, adults with acute, nonspecific low back or neck pain treated with opioids had similar pain relief as those treated with placebo. In patients with knee osteoarthritis who want to participate in sports and recreation, 70 to 90 minutes of exercise produces better results than 20 to 30 minutes three times per week. Healthy behaviors are associated with a lower risk of developing type 2 diabetes mellitus. In patients 50 years and older with type 2 diabetes, cumulative glycemic control with A1C levels of greater than 9% is associated with an increased risk of dementia. Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists are best for improving patient-oriented outcomes for type 2 diabetes. Mindfulness-based stress reduction is not inferior to escitalopram in adults with anxiety disorders. Framing depression as an adaptation to current circumstances can lead to better patient outcomes. People labeled as having a penicillin allergy can complete an amoxicillin oral provocation challenge in the primary care office and, following a negative result, have this label removed. A 5-year surveillance interval can be safely reconsidered in many older patients with colon polyps. Nonprescription hearing aids can be effective without a fitting by an audiologist. We wrap this up with the top guidelines of the year as determined by POEM readers.