Medication reviews focusing on deprescribing can reduce potentially inappropriate medication; however, evidence regarding effects on health‐related outcomes is sparse. In a real‐life quality improvement project using a newly developed chronic care model, we investigated how a general practitioner‐led medication review intervention focusing 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 the 105 included patients, 87 completed the follow‐up. From baseline to follow‐up, 255 medication changes were made, of which 83% were deprescribing. Mean self‐reported health status increased (0.55 [95% CI: 0.22 to 0.87]); the proportion with general condition rated as ‘average or above’ was stable (0.06 [95% CI: −0.02 to 0.14]); and the proportion with functional level ‘without any disability’ was stable (−0.05 [95% CI: −0.09 to 0.001]). In conclusion, this general practitioner‐led medication review intervention was associated with deprescribing and increased self‐reported health status without the deterioration of general condition or functional level in real‐life primary care patients. The results should be interpreted carefully given the small sample size and lack of control group.