Medication reviews focusing on deprescribing can reduce potentially inappropriate medication; however, evidence regarding the effects on health-related outcomes is scares. In a real-life, quality improvement project, we aimed to investigate how a general practitioner-led medication review intervention with focus on deprescribing affected health-related outcomes. We performed a before-after intervention study including care home residents and community-dwelling patients affiliated with a large Danish general practice. The primary outcomes were changes in self-reported health status, general condition, and functional level from baseline to 3-4 months follow-up. Of 105 included patients, 87 completed follow-up. From baseline to follow-up, 255 medication changes were made, of which 83% were deprescribing. Mean self-reported health status increased from 7.3 to 7.9 (0.6 [95% CI: 0.2 to 0.9]); the proportion of patients with general condition rated as “average or above” was stable (74.7% to 80.5% (5.7% [95% CI: -3.4 to 14.9]); and the proportion of patients with functional level “without any disability” was stable (58.6% to 54.0% (-4.6% [95% CI: -10.1 to 1.0]). In conclusion, this general practitioner-led medication review intervention led to deprescribing and increased self-reported health status without deterioration of general condition or functional level in real-life primary care patients.